A  STUDY  OF  METABOLISM  IN 
SEVERE  DIABETES 


BY 


FRANCIS  G,  BENEDICT  and  ELLIOTT  P.  JOSLIN 


WASHINGTON,  D.  C. 

PUBLISHBD  BY  THE  CAHNSJaiB  INSTITUTION  OF  WASHINGTON 

1912 


4  3  I 


A  STUDY  OF  METABOLISM  IN 
SEVERE  DIABETES 


BY 


FRANCIS  G.  BENEDICT  and  ELLIOTT  P.  JOSLIN 


WASHINGTON,  D.  C. 

Published  by  the  Carnegie  Institution  of  Washington 
1912 


Carnegie  Institution  of  Washington 
Publication  No.  176 


PRESS   OF   GIBSON   BROTHERS 
WASHINGTON,  D.  C. 


PREFACE. 


The  researches  in  this  book  are  an  amphfication  of  the  investigation  on 
the  metabohsm  of  diabetes  melhtus  instituted  in  this  laboratory  in  1908.  The 
experimental  evidence  has  reached  such  a  point  that  certain  fundamental 
questions  can  be  adequately  discussed;  many  others  are  still  in  the  process  of 
investigation. 

The  complicated  nature  of  calorimetric  experiments,  the  urine  analyses, 
and  the  respiration  experiments  have  made  this  study  possible  only  through 
the  active  and  hearty  cooperation  of  our  associates.  Most  of  the  respiration 
and  calorimeter  experiments  were  made  either  by  Mr.  Thome  M.  Carpenter 
or  Mr.  L.  E.  Emmes.  The  urinary  analyses  were  made  in  part  in  the  Nutri- 
tion Laboratory  and  in  part  in  the  private  laboratory  of  one  of  us  (E.  P.  J.), 
with  frequent  determinations  in  both  places  as  controls.  As  before,  the  deter- 
minations of /S-oxybutyric  acid  were  made  by  Dr.  F.  H.  Stanwood  in  the  Lab- 
oratory of  Biological  Chemistry  of  the  Harvard  Medical  School.  The  routine 
clinical  urinary  examinations  were  made  by  Miss  Elsie  Newman,  while  the 
total  nitrogen  determinations  and  the  sugar  determinations  by  the  copper- 
reduction  method  were  made  in  the  Nutrition  Laboratory  by  Miss  Alice 
Johnson  and  Miss  E.  B.  Babcock. 

For  the  determinations  of  the  "retention  of  alkali"  by  the  kidneys  in  the 
case  of  a  normal  individual  studied  in  connection  -wdth  this  report  we  are 
indebted  to  Dr.  Gerald  Blake. 

Nutrition  Laboratory  of  the  Carnegie  Institution  of  Washington, 

Boston,  Mass.,  June  I4,  1912. 


209181 


CONTENTS. 


Page. 

Part  I. — Introduction 3 

Plan  of  research 4 

Apparatus  and  methods 7 

Determination  of  gaseous  tensions  of  aveolar  air 7 

Ventilation  of  the  lungs 7 

Determination  of  sugar  in  the  urine 8 

A  copper-reduction  method  of  sugar  analysis  (A.  W.  Peters) 8 

The  heating  power 8 

The  process  of  reduction 9 

The  determination  of  reduced  copper 10 

The  control  of  all  of  the  conditions 11 

Calorimetric  measurements 12 

Part  II. — Statistics  of  experiments  on  the  metabolism  of  diabetics 15 

Classification  of  cases 15 

Diet 16 

List  of  experiments  with  diabetics 16 

Case  A 17 

Case  B 18 

Case  G 19 

Case  H 19 

Case  1 21 

Case  J 23 

Case  K 24 

Case  L 25 

Case  M 27 

Case  N 29 

Case  O 36 

Case  P 41 

Case  Q 51 

Case  R 55 

Case  S 61 

Case  T 63 

Case  U 66 

Case  V 75 

Case  W .  76 

Case  X 79 

Part  III. — Discussion  of  results  and  general  conclusions 85 

Pulse-rate 85 

Body-temperature 87 

Body-weight 89 

Nitrogen  excretion  of  diabetics  without  food 102 

Gaseous  metabolism 104 

Carbon-dioxide  excretion  in  diabetes 104 

Oxygen  consimiption  in  diabetes 107 

V 


VI  CONTENTS. 

Page. 
Discussion  of  results  and  general  conclusions — Continued. 
Gaseous  metabolism — Continued. 

Respiratory  quotient 110 

Indirect  calorimetry 113 

Composition  of  the  alveolar  air  of  diabetics 114 

Comparison  of  the  metabolism  of  diabetics  with  that  of  normal  individuals 117 

Selection  of  controls 118 

Evidence  of  the  kymograph  record 118 

Detailed  comparison  of  normals  and  diabetics 119 

Comparison  of  the  metabolism  of  diabetics  with  varying  degrees  of  severity.  .  .  122 
A  comparison  of  the  metabolism  of  fasting  diabetics  under  varying  conditions  as 

to  the  intensity  of  the  acidosis 123 

The  influence  of  a  normally  induced  acidosis  upon  metabolism 125 

Experiments  with  H.  L.  H 126 

Statistics  of  experiments  with  H.  L.  H 126 

Results  of  experiments  with  H.  L.  H 127 

Experiments  with  H.  H.  A 128 

Statistics  of  experiments  with  H.  H.  A 129 

Results  of  experiments  with  H.  H.  A 132 

Relations  between  a  normally-induced  acidosis  and  the  observed  increase  in 

the  metabohsm  in  severe  diabetes 134 


A  STUDY  OF  METABOLISM  IN  SEVERE 

DIABETES 


BY 

FRANCIS  G.  BENEDICT  and  ELLIOTT  P.  JOSLIN 


PART  I. 

INTRODUCTION. 

It  is  acknowledged  by  all  clinicians  that  the  most  satisfactory  treatment 
of  diabetes  meilitus  is  obtained  by  a  careful  and  intelligent  regulation  of  the 
diet.  The  use  of  drugs  has  invariably  met  with  but  transitory  success;  modern 
clinicians  are  therefore  relying  less  and  less  upon  such  remedies  and  are  turning 
their  attention  more  definitely  toward  a  careful  dietetic  regime.  Accordingly 
it  is  of  fundamental  importance  that  all  the  knowledge  possible  should  be  care- 
fully accumulated  regarding  the  uses  made  by  the  diabetic  patient  of  the  diet, 
the  demands  of  the  body  for  nutriment,  and  the  best  kinds  of  food  to  be 
ingested.  It  is  of  further  importance  that  the  reaction  of  the  healthy  indi- 
vidual to  the  narrow  diet  of  the  diabetic  should  be  investigated,  and  this  espe- 
cially because  the  studies  upon  acidosis  have  shown  that  the  metabolism  of 
health  may  be  made  to  closely  approximate  that  of  disease  by  simple  external 
influences,  such  as  the  withdrawal  of  all  carbohydrate  and  the  excessive  admin- 
istration of  fat. 

In  our  earlier  investigation^  we  endeavored  to  study  the  energy  transfor- 
mations of  diabetics  without  giving  particular  attention  to  the  influence  of  the 
intake  of  food.  It  was  believed  that  the  energy  transformations  without  food 
should  first  be  clearly  established,  and  then  a  study  should  be  made  of  the  influ- 
ence of  various  foods  upon  the  metabolism  of  diabetics,  with  particular  refer- 
ence to  the  effect  of  the  so-called  "oatmeal  cure,"  which  has  received  much 
attention  in  recent  years. 

Although  the  method  of  study  has  not  been  materially  modified  in  our 
later  observations  now  to  be  recorded,  our  experience  in  the  first  series  has 
enabled  us  to  plan  to  better  advantage  each  individual  experiment  with  the 
purpose  of  making  it  an  improvement  upon  those  preceding.  Careful  atten- 
tion to  experimental  details,  a  most  scrupulous  regulation  of  the  diet,  and  the 
technical  experience  acquired  in  the  last  three  years  in  numerous  experiments 
of  this  type  with,  both  normal  and  pathological  individuals  have  all  helped  to 
raise  somewhat  the  standard  of  accuracy  and  give  us  increased  confidence  in 
the  correctness  of  the  plan  of  procedure.  In  the  earlier  investigation  as  many 
individuals  as  possible  were  studied  in  order  to  determine  their  general  energy 
requirement  for  comparison  with  the  energy  requirement  of  normal  individuals; 
in  the  later  series  of  observations  the  attempt  was  made  to  study  systemati- 
cally and  completely  the  individual  subjects  rather  than  to  make  a  large  number 
of  less  detailed  observations  on  a  variety  of  subjects.  At  least  three  of  the 
cases  reported  herewith  have  been  most  carefully  studied  over  a  considerable 
period  of  time. 


^Benedict  and  Joslin,  Metabolism  in  Diabetes  Meilitus,  Carnegie  Institution  of  Wash- 
ington Publication  No.  136,  1910. 

3 


4  METABOLISM   IN   SEVERE   DIABETES. 

The  fundamentally  vital  conclusion  of  our  first  report,  i.  e.,  that  the 
metabolism  of  diabetics  was  increased  above  normal  somewhat  over  15  per 
cent,  was  not  readily  accepted,  as  was,  perhaps,  natural,  and  criticisms  of  the 
methods,  particularly  of  the  method  of  comparison  of  diabetics  with  normals, 
were  freely  made.  While  we  believe  that  the  earlier  results  showed  definitely 
that  our  conclusion  was  well  founded,  the  fact  that  the  criticisms  raised  were 
made  by  a  number  of  excellent  workers  in  the  field  of  metabolism  justified  our 
continuing  the  accumulation  of  experimental  evidence.  As  a  result  of  this 
later  work,  we  find  ample  confirmation  of  the  conclusion  drawn  from  our  ear- 
lier investigations,  namely,  that  the  metabolism  of  diabetics  was  increased 
(about  15  per  cent)  above  normal.  The  criticisms  raised  by  a  number  of 
writers  with  regard  to  this  general  thesis  are  discussed  in  Part  III. 

In  our  first  report  the  principal  subjects  considered  were  the  energy  trans- 
formations and  gaseous  exchange  of  diabetics.  Incidentally  evidence  was 
presented  regarding  the  dextrose-nitrogen  ratio  and  the  ingestion  of  food.  In 
discussing  the  influence  of  the  ingestion  of  beefsteak  upon  the  metabolism  of 
one  of  the  subjects  we  were  entirely  at  fault  in  our  statements  regarding  the 
dextrose-nitrogen  ratio — an  error  that  has  been  clearly  pointed  out  by  Lusk.^ 

On  the  other  hand,  we  see  no  reason  to  alter  our  opinion  there  expressed 
that  with  diabetics  the  dextrose-nitrogen  ratio  is  at  best  a  very  uncertain  factor, 
and  unless  a  rigidly  strict  carbohydrate-free  diet  be  adhered  to  for  several 
days,  the  dextrose-nitrogen  ratios  have  little,  if  any,  significance.  Neither  do 
we  see  any  reason  for  changing  our  belief  that  the  adherence  to  a  strictly 
carbohydrate-free  diet  in  severe  diabetes  during  a  period  of  several  days  is  a 
procedure  very  much  to  be  questioned.  This  being  the  case,  the  significance 
of  the  dextrose-nitrogen  ratio  for  diagnostic  purposes  has  not,  we  believe,  the 
importance  that  has  been  ascribed  to  it  by  other  writers. 

Plan  of  Research. 

The  original  plan  of  research  involved  the  study  of  a  number  of  different 
problems.  Of  these,  the  first  was  the  accumulation  of  further  evidence  with 
regard  to  the  increase  in  metabolism  noted  with  practically  all  of  the  diabetics 
previously  studied.  The  difficulty  incidental  to  a  satisfactory  comparison  of 
diabetics  with  normal  subjects  was  pointed  out  in  great  detail  in  the  first  report, 
and  while  we  firmly  believe  that  the  evidence  there  set  forth  showed  that  on 
the  average  there  was  an  increase  in  metabolism  of  15  per  cent  in  diabetes  over 
health,  nevertheless  plausible  arguments  could  be  brought  forward  indicating 
that  the  comparison  of  diabetics  with  normal  subjects  might  not  be  scientif- 
ically sound  or  correct.  The  disproportion  between  the  body-weight  and  the 
body-surface  of  the  two  classes  of  subjects,  the  differences  in  the  kinds  of  food 
eaten,  the  possibility  of  a  larger  protein  katabolism  with  diabetics,  and  the 
error  of  drawing  deductions  from  one  individual  as  normal  and  another  indi- 
vidual as  a  diabetic  are  by  no  means  convincing  arguments  against  our  thesis; 

^Lusk,  Science,  33,  p.  433. 


INTRODUCTION.  5 

nevertheless  they  remain  as  possible  and  plausible  criticisms  of  the  conclusion 
drawTi  from  our  earlier  work.  The  later  experiments  were  therefore  planned 
further  to  clarify  the  situation  and  to  remove  cause  for  criticism. 

It  also  became  necessary  to  secure  additional  data  with  regard  to  nor- 
mal individuals.  During  the  progress  of  this  investigation  a  large  number  of 
normal  subjects  have  been  studied  in  connection  with  the  respiration  researches 
in  this  laboratory,  and  hence  the  data  are  continually  increasing.  They  will 
here  be  presented  in  abstract  to  show  normal  metabolism  under  conditions  of 
experimentation  similar  to  those  used  with  the  diabetics  studied. 

Furthermore,  a  study  of  the  influence  of  the  ingestion  of  carbohydrates 
upon  the  metabolism  of  diabetics  was  deemed  of  great  importance.  The 
early  investigations  of  Nehring  and  SchmolV  Magnus-Levy,^  and  Leo^  indi- 
cated that  with  the  ingestion  of  carbohydrates  there  was  frequently  no  increase 
in  the  respiratory  quotient.  Similarly  there  was  apparently  no  great  increase 
in  the  sugar  excreted  in  the  urine;  at  least  the  increase  was  not  suJfificient  to  off- 
set the  excess  carbohydrate  ingested;  and  while  there  may  have  been  a  posi- 
tive carbohydrate  balance  on  that  particular  day,  the  respiratory  exchange  did 
not  indicate  a  combustion  of  carbohydrates,  since  it  was  not  materially  higher 
than  during  fasting.  This  presented  an  anomalous  situation  in  that  while 
carbohydrate  was  ingested  in  large  amounts,  it  apparently  was  neither  burned 
nor  excreted,  and  the  question  therefore  immediately  arose  as  to  where  this 
carbohydrate  had  disappeared.  For  the  purpose  of  throwing  light  upon  the 
problem  a  number  of  experiments  were  made  in  this  laboratory  in  which  vari- 
ous carbohydrates  were  ingested,  chiefly  levulose  and  oatmeal,  the  latter  being 
used  particularly  on  account  of  the  great  interest  in  the  so-called  "oatmeal 
cure"  for  diabetes.  Under  these  conditions  the  metabolism  was  studied  very 
exactly  in  short  periods  following  the  ingestion  of  various  amounts  of  carbo- 
hydrates in  order  to  determine  whether  there  was  an  increase  in  the  metabolism 
or  a  variation  in  the  respiratory  quotient  which  would  indicate  a  difference  in 
the  character  of  the  metabolism  as  the  time  progressed.  In  this  way  it  w^as 
hoped  that  some  hght  would  be  thrown  upon  the  character  of  the  metabolism 
and  the  apparent  storage  of  carbohydrate. 

In  at  least  one  or  two  of  the  earlier  experiments  we  found  an  apparently 
abnormal  reaction  to  the  ingestion  of  protein.  With  normal  individuals  the 
ingestion  of  protein,  particularly  in  the  form  of  beefsteak,  shortly  produces  a 
rise  in  metabolism,  i.  e.,  the  "specific  dynamic  action"  of  the  protein.  With 
one  of  the  cases  previously  reported  (Case  A)  this  rise  in  metabolism  did  not 
appear;  it  was  therefore  suggested  that  possibly  when  the  body  was  extremely 
glycogen-poor  the  non-nitrogenous  portion  of  the  protein  molecule  split  off 
when  the  steak  was  ingested  and  Avas  deposited  as  glycogen  instead  of  being 
burned,  and  that  the  specific  dynamic  action  of  the  protein  might  be  due  to 
the  rapid  combustion  of  the  non-nitrogenous  parts  of  the  protein  molecule.     It 

'Nehring  and  Schmoll,  Zeitschr.  f.  klin.  Med.,  1897,  31,  p.  59. 
«Magnus-Levy,  Zeitschr.  f.  kUn.  Med.,  1905,  56,  p.  86. 
•Leo,  Zeitschr.  f.  klin.  Med.,  1891,  p.  101. 


6  METABOLISM   IN   SEVERE   DIABETES. 

seemed  important  to  verify  this  observation,  if  possible,  by  further  evidence; 
hence  a  number  of  experiments  are  here  included  in  which  beefsteak  was 
ingested. 

Our  earlier  experiments  also  suggested  that  during  severe  acidosis,  when 
the  patients  were  clinically  in  the  worst  condition,  there  was  a  higher  meta- 
bolism. The  relationship  between  the  acidosis  and  metabolism  was  by  no 
means  clearly  established  or,  indeed,  recognized  in  our  earlier  report,  but  as 
these  investigations  progressed,  it  became  desirable  to  make  a  particular  study 
of  the  relationship  between  the  degree  of  acidosis  and  the  total  metabolism. 
This  has  been  given  a  special  and  prominent  part  in  the  later  research,  and 
the  relationship  between  the  degree  of  acidosis  and  the  total  metabolism  has 
proved  to  be  one  of  the  most  interesting  points  in  this  study. 

It  was  possible  so  to  adjust  the  diet  of  the  diabetics  as  to  secure  with  the 
same  subject  degrees  of  acidosis  varying  from  very  severe  to  veiy  light;  hence 
we  have  here  an  opportunity  of  comparing  the  metabolism  of  a  diabetic  with 
a  severe  acidosis  ^vith  his  metabolism  when  without  an  acidosis.  This  has 
proved  to  be  a  great  advantage,  since  the  results  obtained  are  more  strictly 
comparable  than  those  obtained  when  comparing  the  metabolism  of  a  diabetic 
with  a  severe  acidosis  with  that  of  a  normal  subject  without  acidosis. 

The  general  plan  of  the  research  as  outlined  in  the  preceding  pages  was 
that  upon  which  the  year's  work  was  based,  but  it  became  clear  as  time  went 
on  that  the  program  must  be  so  restricted  as  to  settle  absolutely  one  or  two 
fundamentally  important  points  rather  than  to  attempt  to  secure  conclusive 
evidence  on  so  many  different  phases  of  the  question  as  are  here  outlined. 
While  it  was  thoroughly  practicable  to  secure  evidence  with  regard  to  the 
increased  metabolism  during  different  degrees  of  severity  of  diabetes,  and  while 
the  relationship  between  the  severity  of  diabetes  and  the  metabolism  began  to 
be  strikingly  apparent,  nevertheless,  for  experiments  on  the  ingestion  of  oat- 
meal, carbohydrates,  and  beefsteak,  both  a  certain  type  of  case  and  a  certain 
type  of  experimental  plan  were  necessary.  For  this  reason  it  was  more  diffi- 
cult to  secure  patients  for  this  series  of  experiments  than  for  a  study  of  the  gen- 
eral and  broader  questions;  hence,  while  a  considerable  amount  of  data  has 
been  accumulated  on  the  points  here  raised,  we  do  not  presume  in  this  report 
to  discuss  in  any  way  the  questions  with  regard  to  the  influence  of  the  inges- 
tion of  food,  the  dextrose-nitrogen  ratio,  the  influence  of  the  ingestion  of  car- 
bohydrates and  sugars  upon  the  positive  carbohydrate  balance,  and  similar 
questions,  except  in  a  very  general  way  incidental  only  to  their  effect  upon  the 
question  of  the  relation  between  the  severity  of  the  diabetes  and  the  general 
metabolism.  On  the  other  hand,  it  seems  desirable  to  present  in  this  report 
all  of  the  statistical  data  for  the  experiments  thus  far  made,  so  as  to  make  them 
available  for  clinicians  and  for  scientists  interested  in  metabolism  during  dia- 
betes. A  complete  discussion  of  the  data,  together  with  additional  material, 
will  be  given  in  a  subsequent  publication. 

Consequently  the  final  plan  of  work  considered  in  this  report  will  be  first, 
the  evidence  with  regard  to  the  increased  metabofism  during  diabetes;  second, 


INTRODUCTION.  7 

the  relationship  between  the  severity  of  diabetes  and  the  degree  of  increased 
metaboHsm;  and  third,  the  influence  of  a  carbohydrate-free  diet  upon  the  total 
metabolism  of  normal  individuals.  Incidentally  the  accumulated  data  jus- 
tify the  discussion  of  the  factors  affecting  body-weight.  In  connection  with 
the  research  a  modified  method  for  the  rapid  quantitative  determination  of 
sugar  in  the  urine  has  been  elaborated  which  is  described  at  some  length. 

Apparatus  and  Methods. 

The  apparatus  and  methods  used  in  the  conduct  of  this  research  are  essen- 
tially those  described  in  the  earlier  publication.^  The  bed  calorimeter  has 
been  more  extensively  employed  than  has  the  chair  calorimeter,  the  latter 
being  used  for  only  three  experiments  in  this  connection.  On  the  other  hand, 
the  respiration  apparatus,  which  has  continually  undergone  minor  modifica- 
tions in  methods  of  technique  and  facility  of  operation,  though  not  in  principle, 
has  been  extensively  used.^  In  most  instances  it  has  been  found  that  observa- 
tions made  with  this  apparatus  are  fully  as  valuable  and  essentially  the  same 
as  are  the  more  time-consuming  and  expensive  observations  with  the  respi- 
ration calorimeter;  hence  we  have  no  doubt  of  the  wisdom  or  propriety  of  com- 
puting the  energy  transformations  from  the  gaseous  metabolism  as  determined 
on  the  respiration  apparatus.  The  respiration  apparatus  has  the  special 
advantage  in  that  with  it  experiments  can  be  made  rapidly,  and  thus  the  time 
relations  of  the  metabolism,  particularly  after  the  ingestion  of  food,  can  be 
more  exactly  and  rapidly  studied  than  in  experiments  with  the  respiration 
calorimeter,  with  the  longer  periods  of  45  minutes. 

DETERMINATION  OF  GASEOUS  TENSIONS  OF  ALVEOLAR  AIR. 

Owing  to  the  interesting  observations  of  Beddard,  Pembrey  and  Spriggs,^ 
it  seemed  advisable  in  certain  instances  to  determine  the  composition  of  the 
alveolar  air  in  severe  cases  of  diabetes.  Accordingly,  with  three  subjects 
(I,  N,  and  Q)  observations  were  made  of  the  carbon-dioxide  tension,  and  at 
times  the  oxygen  tension,  of  the  alveolar  air,  these  being  in  large  part  carried 
out  through  the  kindness  of  Mr.  H.  L.  Higgins,  of  the  laboratory  staff,  who 
used  the  Haldane  gas-analysis  apparatus^  and  both  the  Haldane  and  the  Plesch 
methods  for  determining  the  alveolar  air.^ 

VENTILATION  OF  THE  LUNGS. 

Using  an  Elster  meter  of  the  type  employed  by  Zuntz,  and  a  pair  of  Zuntz 
valves,  the  ventilation  of  the  lungs  per  minute  was  also  occasionally  deter- 
mined with  one  of  the  subjects  (N). 

^Benedict  and  Joslin,  loc.  ciL,  p.  15. 

^A  detailed  description  of  the  apparatus,  showing  its  use  and  technique,  has  just  been 
published  in  the  Deutsch.  Archiv.  f.  klin.  Med.,  1912,  107,  p.  156. 

^Beddard,  Pembrey  and  Spriggs,  Proe.  Physiol.  Soc,  Journ.  Physiol.,  1908,  37,  p.  39. 

^Haldane,  Methods  of  air  analysis,  London,  1912. 

'Haldane  and  Priestley,  Journ.  Physiol.,  1905,  32,  p.  225;  Plesch,  Zeitschr.  f.  Exp. 
Pathol,  u.  Ther.  1909,  6,  p.  380. 


8  METABOLISM   IN   SEVERE   DIABETES. 

DETERMINATION  OF  SUGAR  IN  THE  URINE. 

General  dissatisfaction  with  the  methods  commonly  used  for  the  estima- 
tion of  reducing  sugars  was  expressed  in  our  first  report  and  it  was  there  pointed 
out  that  the  newly-introduced  Citron  method,  while  of  value  from  the  clinical 
standpoint,  was  of  little  value  from  the  standpoint  of  exact  scientific  research. 
In  our  new  experiments  the  Citron  method  was  used  for  only  the  earlier  deter- 
minations of  sugar.  Those  made  in  the  private  laboratory  of  E.  P.  J.  were  for 
the  most  part  carried  out  by  a  method  suggested  by  Dr.  Stanley  R.  Benedict,^ 
of  the  Cornell  University  Medical  College.  For  the  more  recent  analyses, 
especially  those  made  in  connection  with  the  best  experiments,  a  highly 
improved  method  was  used  which  was  devised  by  Dr.  A.  W.  Peters,  of  the 
Nutrition  Laboratory.  After  a  most  careful  study  of  the  conditions  affecting 
reduction,  temperature  conditions,  and  concentration.  Dr.  Peters  developed  a 
method  using  the  old  Fehling  or  Allihn  solution  of  copper  sulphate  and  the 
alkaline  tartrate,  and  has  determined  the  amount  of  unreduced  copper  remain- 
ing in  the  solution  by  a  titrimetric  method.  By  this  means  the  most  accurate 
determinations  of  sugar  are  possible,  this  being  without  doubt  the  most  exact 
method  of  sugar  determination  that  has  thus  far  been  devised.  While  the 
method  may  be  readily  used  in  hospital  laboratories,  it  will  probably  never  be 
acceptable  for  private  practice.  Inasmuch  as  it  represents  the  most  scientific 
attempt  to  study  quantitatively  the  method  of  sugar  reduction,  it  is  given 
herewith  in  considerable  detail.  For  this  presentation  of  the  method  we  are 
indebted  to  its  author,  Dr.  A.  W.  Peters. 

A  COPPER-REDUCTION  METHOD  OF  SUGAR  ANALYSIS  (a.  W.  PETERS). 

The  construction  of  this  method  of  sugar  analysis  is  based  upon  preceding 
developments  for  (1)  the  accurate  volumetric  determination  of  copper  in  alka- 
line tartrate  liquids;  (2)  the  standardization  of  the  heating  power  used;  and  (3) 
the  determination  of  constant  and  controllable  conditions  for  the  reduction. 
For  more  detail  reference  must  be  made  to  the  original  descriptions.^  When 
the  apparatus  and  reagents  have  once  been  prepared  a  single  determination 
occupies  from  12  to  15  minutes. 

The  Heating  Power. 

A  heating  apparatus  should  be  set  up  of  such  power  that  it  will  heat 
60  c.c.  of  distilled  water  under  described  conditions  through  the  temperature 
interval  of  35°  to  95°  C.  in  120  seconds  ±  5  seconds.  The  water  is  placed  in  an 
Erlenmeyer  flask  of  the  best  Jena  glass,  with  a  capacity  of  about  200  cm.  and  a 
basal  diameter  of  about  6  cm.,  so  that  the  depth  of  the  liquid  will  be  about  18 
mm.     The  flask  is  partially  closed  with  a  two-hole  stopper,  one  hole  of  which 

^Dr.  S.  R.  Benedict's  method  is  based  upon  the  reducing  action  of  sugars  upon  an 
alkahne  sulphocyanate  solution  of  copper.     See  Benedict,  Journ.  Biol.  Chem.,  1911,  9,  p.  57. 

'Peters,  Amos  W.,  The  sources  of  error  and  the  electrolytic  standardization  of  the  iodide 
method  of  copper  analysis,  Journ.  Am.  Chem.  Soc,  1912,  34,  pp.  422;  and  A  critical  study 
of  sugar  analysis  by  copper-reduction  methods,  Journ.  Am.  Chem.  Soc,  1912,  34,  p.  928. 


INTRODUCTION.  9 

carries  a  thermometer.  The  thermometer  should  not  have  a  greater  error  at 
the  boiUng-point  of  water  than  ±0.5°  C.  when  the  barometric  pressure  is  taken 
into  consideration.  The  lower  end  of  the  thermometer  should  be  placed  at  a 
distance  of  about  2  mm.  from  the  bottom  of  the  flask  and  the  region  of  the  stem 
above  35°  C.  should  extend  above  the  upper  surface  of  the  stopper  so  as  to  be 
plainly  visible.  This  flask  should  be  placed  in  the  center  of  a  plate  of  unper- 
forated  asbestos  gauze  carried  by  a  ring-stand  so  that  it  can  be  raised  or  low- 
ered. The  distance  between  the  burner  and  the  asbestos  should  always  fall 
within  the  limits  of  3  to  5  cm.,  thus  avoiding  a  long  flame  which  would  be  easily 
affected  by  air-currents.  Room-temperature  and  freedom  from  drafts  should 
prevail.  If  the  latter  condition  can  not  be  provided  the  heating  apparatus 
may  be  wholly  or  partially  protected  by  a  cylindrical  hood  of  sheet  metal  or 
asbestos.  The  flask  as  above  described  containing  60  c.c.  of  distilled  water 
is  placed  on  the  asbestos  and  the  time  observed  that  is  required  for  the  mer- 
cury to  rise  from  35°  to  95°  C.  The  rough  adjustment  to  120  seconds  is  made 
by  regulating  the  flow  of  gas  so  as  to  change  the  power  of  the  flame  with  the 
position  of  the  asbestos  constant  at  4  cm.  The  finer  adjustment  is  made  by 
moving  the  asbestos  plate  toward  or  away  from  the  burner  within  the  limits  of 
3  to  5  cm.  The  conditions  are  not  properly  adjusted  until  repeated  determina- 
tions of  the  time  give  constant  results  within  limits  of  error  of  only  a  few 
seconds.  At  120  seconds  the  standard  heating  power  here  adopted  has  been 
established. 

The  Process  of  Reduction. 

The  reduction  mixtures  should  be  placed  in  the  same  kind  of  flasks,  with 
the  same  stopper,  thermometer,  etc.,  and  with  the  same  conditions  of  heating 
power  as  were  used  for  the  standardization  of  the  latter.  The  volume  of  the 
reduction  mixture  is  always  60  c.c.  It  consists  of  20  c.c.  of  Allihn's  alkaline 
tartrate  solution  plus  20  c.c.  of  Fehling's  copper  sulphate  solution  plus  20  c.c. 
of  distilled  water  for  a  blank  determination,  or,  in  the  case  of  sugar  analysis,  of 
an  aqueous  sugar  solution  with  enough  distilled  water  added  to  make  a  final 
volume  of  60  c.c. 

The  Fehling-Soxhlet  solution  contains  34.639  grams  of  pure  crystallized 
copper  sulphate  in  a  volume  of  500  c.c,  but  the  purity  of  the  copper  sulphate 
is  more  important  than  its  exact  weight.  Since  its  correct  copper  content  can 
not  with  reliability  be  deduced  from  the  formula  CUSO4.5H2O,  this  value  is 
found  by  means  of  standardized  thiosulphate  as  described  on  page  11  for  the 
"basis  titration."  The  Allihn  alkaline  tartrate  solution  contains  173  grams  of 
sodium-potassium  tartrate  (Rochelle  salt)  and  125  grams  of  potassium  hydrox- 
ide in  a  volume  of  500  c.c. 

For  a  determination  of  sugar  the  flask  containing  the  reduction  mixture  is 
placed  on  the  heating  apparatus  and  the  time  is  observed,  but  in  this  case  the 
reckoning  begins  only  when  the  thermometer  reaches  95°  C.  The  flask  should 
stand  undisturbed  in  the  center  of  the  asbestos  gauze  until  the  expiration  of  20 
seconds  after  the  temperature  of  95°  C.  has  been  reached.  It  is  then  promptly 
removed,  with  the  stopper  and  thermometer  still  in  place,  and  twirled  for  a  few 


10  METABOLISM   IN   SEVERE   DIABETES. 

seconds  under  the  tap  in  order  to  cool  the  mixture  rapidly,  but  only  to  a  few 
degrees  under  the  boiUng-point,  since  the  mixture  is  to  be  filtered  hot  without 

delay. 

A  Gooch  crucible  should  have  been  previously  prepared  with  a  very  heavy 
filter,  so  that  suction  will  draw  water  through  it  only  slowly.  Avery  close  and 
satisfactory  filter  may  be  made  by  placing  a  layer  of  pure  talcum  powder 
between  two  layers  of  asbestos  in  the  Gooch  crucible.  A  good  filter  may  also 
be  made  by  substituting  for  the  crucible  a  calcium-chloride  drying-tube  car- 
ried by  a  one-hole  rubber  stopper.  This  is  packed  first  with  glass-wool  and 
upon  this  is  made,  in  the  bulb  of  the  tube,  a  very  heavy  mat  of  asbestos,  which 
may  also  be  made  as  close  as  desired  by  means  of  talcum.  The  same  filter  is 
used  many  times,  the  precipitate  being  removed  from  it  by  nitric  acid  (original 
specific  gravity  of  1.42)  which  has  been  diluted  with  one-half  of  its  volume  of 
distilled  water.  This  requires  less  time  than  making  a  new  filter  for  each  deter- 
mination. The  suction-flask  should  have  a  capacity  of  about  200  c.c,  so  that 
a  titration  on  the  filtrate  can  be  performed  in  the  suction-flask,  thus  avoiding  a 
transfer  of  the  hquid.  Not  more  than  15  to  20  c.c.  of  wash-water  should  be 
used,  as  it  all  remains  as  part  of  the  final  volume  at  the  end  of  titration.  This 
volume  should  not  exceed  120  c.c,  to  which  volume  the  concentration  of  the 
reagents  used  for  the  determination  of  copper  has  been  adjusted.  For  the 
inexperienced  it  is  recommended  to  make  a  rough  measurement  of  the  final 
volume  of  the  liquid  obtained  at  the  end  of  titration. 

The  Determination  of  Reduced  Copper. 

The  amount  of  copper  that  has  been  reduced  under  the  above  conditions  is 
a  quantitative  index  of  the  amount  of  sugar  originally  present.  The  reduced 
copper  may  be  determined  directly  upon  the  precipitated  cuprous  oxide  or 
residually  by  the  determination  of  the  amount  of  copper  still  remaining  un- 
reduced in  the  alkaline  filtrate.  The  amount  of  copper  in  the  filtrate  may  be 
determined  either  electrolytically  for  control  or  volumetrically  by  the  iodide 
method.  For  rapidity  combined  with  accuracy  the  iodide  method  is  recom- 
mended, but  only  when  it  has  first  been  controlled  for  the  conditions  under 
which  it  is  to  be  used.  For  the  alkaline  tartrate  copper  solutions  Avhich  are 
here  used  (i.  e.,  Allihn's  alkaline  tartrate,  etc.)  this  control  has  been  satisfac- 
torily made.  The  residual  method  for  the  determination  of  the  reduced  copper 
may  therefore  be  regarded  as  certainly  the  most  rapid  as  well  as  accurate  when 
the  iodide  method  is  applied  as  described  in  the  previous  references  and  under 
the  following  provisions : 

(1)  The  thiosulphate  solution  should  have  a  value  between  12.5  and  13 
mg.  of  copper  per  cubic  centimeter.  It  should  be  standardized  preferablj^ 
against  the  same  stock  solution  of  copper  which  is  to  be  used  in  the  sugar 
analyses,  and  the  true  copper  value  of  this  solution  should  be  determined  elec- 
trolytically. If,  however,  the  stock  solution  is  made  of  chemically  pure  copper 
sulphate  there  will  be  no  appreciable  difference  between  the  standard  value  of 
the  thiosulphate  determined  by  this  electrolytically  controlled  solution,  and  the 
value  obtained  by  the  nitric-acid-talcum  procedure  above  referred  to,  using 


INTRODUCTION.  11 

pure  metallic  copper,  which  procedure  may  then  be  substituted  for  electrolytic 
determination  on  the  stock  solution.  The  standardization  may  appropriately 
be  made  on  20  c.c.  of  the  stock  solution,  which  is  the  same  volume  as  will  be 
used  in  sugar  determinations,  and  with  a  final  volume  at  the  end  of  titration  in 
no  case  exceeding  120  c.c.  This  volume  should  contain  20  c.c.  of  concentrated 
acetic  acid  and  about  7  c.c.  of  saturated  solution  of  pure  potassium  iodide. 
The  thiosulphate  value  of  20  c.c.  of  the  stock  solution  of  copper  sulphate  deter- 
mined in  simple  acetic-acid  solution  is  designated  as  the  "basis  titration,"  and 
is  of  fundamental  importance  for  subsequently  testing  the  constancy  of  solu- 
tions and  of  conditions  even  when  it  is  not  used  for  the  purpose  of  standardi- 
zation. A  solution  of  pure  copper  sulphate  will  remain  at  a  constant  standard 
value,  but  the  thiosulphate  will  change  somewhat  if  much  exposed  to  air  and 
especially  to  light. 

(2)  The  alkaline  filtrates  from  sugar  determinations,  whose  volume  must 
not  exceed  75  c.c,  should  be  acidified  with  concentrated  sulphuric  acid.  The 
amount  of  acid  used  should  be  such  that  the  thiosulphate  value  of  a  blank 
determination,  in  which  the  unheated  reduction  mixture  of  60  c.c.  previously 
described  contains  all  the  reagents  but  no  sugar,  \v\\\  be  identical  with  the 
"basis  titration."  This  amount  has  been  found  by  experiment,  as  described 
in  the  previous  references,  to  be  4  c.c.  of  concentrated  sulphuric  acid,  but  should 
be  verified  or  changed  if  necessary. 

After  the  mixture  has  been  acidified  and  cooled  to  20° C,  potassium  iodide 
is  added  to  the  amount  of  6  to  7  c.c.  of  an  aqueous  solution  that  is  saturated 
at  room-temperature.  The  iodine  which  is  evolved  is  titrated  at  once  with 
thiosulphate,  using  a  solution  of  soluble  starch  as  an  indicator  near  the  close  of 
the  titration.  The  end  point  should  be  determined  by  the  "spot  test,"  espe- 
cially in  the  presence  of  urinary  or  other  coloring  matter,  and  may  be  verified 
by  immediate  back  titration  with  a  drop  of  iodine  solution  of  about  the  same 
concentration  as  the  thiosulphate. 

(3)  For  the  residual  method  a  blank  determination  is  ahvays  necessary. 
The  assumption  that  there  is  no  self-reduction  of  reagents  may  lead  to  error, 
although  by  the  present  method  pure  and  especially  freshly  prepared  reagents 
show  a  negligibly  small  self-reduction.  The  blank  value  is  obtained  with  the 
reduction  mixture  of  60  c.c.  previously  described  but  without  the  presence  of 
sugar.  This  is  heated  and  filtered  and  treated  in  all  respects  as  when  a  deter- 
mination of  sugar  is  made.  From  the  thiosulphate  value  of  the  copper  thus 
found  unreduced  is  subtracted  the  value  found  in  the  same  way  in  a  subsequent 
sugar  analysis.  This  thiosulphate  difference  evidently  shows  the  amount  of 
reduced  copper  due  to  the  action  of  the  sugar.  The  difference  may  be  con- 
verted into  milligrams  of  copper  by  means  of  the  standard  value  of  the  thiosul- 
phate previously  obtained,  and  the  corresponding  amount  of  sugar  may  be 
found  from  a  table  of  reduction  values. 

The  Control  of  All  of  the  Conditions. 

All  of  the  conditions  of  this  method  and  the  technique  of  the  operator  can 
be  controlled  by  the  use  of  a  standard  solution  of  pure  dextrose.     The  results 


12 


METABOLISM   IN   SEVERE   DIABETES. 


thus  obtained  are  a  standard  of  comparison  to  determine  whether  in  a  given 
case  the  conditions  have  been  correctly  adjusted  for  the  use  of  the  values  for 
dextrose  which  are  recorded  in  table  1.  From  these  controls  the  values  for  50 
and  100  mg.  obtained  from  a  0.5  per  cent  or  1  per  cent  standard  solution  of 

pure  dextrose  were  usually  selected  for  the  first  tests.     The  quantities  to  be 

DsxtrosG 
compared  should  be  the   q^         ratios,  as  the  limits  of  error  of  these  are  evi- 
dent from  the  table. 

Table  1. — Reduclion  values  for  dextrose. 


I. 

II. 

III. 
Dextrose- 

I. 

II. 

III. 
Dextrose- 

Dextrose. 

Copper. 

copper 
ratio.  1 

Dextrose. 

Copper. 

copper 
ratio.' 

mg. 

mg. 

mg. 

mg. 

1 

1.2±0.13 

0.833 

60 

115.5 

0.520 

2 

2.8±0.1 

.714 

70 

134.4 

.521 

5 

8.2±0.14 

.610 

80 

152.9 

.523 

8 

13.8±0.1 

.580 

90 

171.0 

.514 

10 

17.4±0.3 

.575 

100 

191.6±0.35 

.522 

15 

27.7±0.5 

.542 

110 

208.9±0.15 

.527 

20 

37.1±0.2 

.539 

120 

228.1 

.526 

25 

48.1±0.4 

.520 

135 

255.0 

.529 

30 

57.3±0.05 

.524 

150 

280.8±0.6 

.5.34 

35 

67.6±0.13 

.518 

165 

306  8 

.538 

40 

76.2±0.1 

.525 

180 

330.5±0.1 

.545 

45 

86.0±0.1 

.523 

200 

349.6 

.572 

50 

96.0±0.5 

.521 

'Average  factor  between  48  and  192  mg.  copper,  0.522. 


Dextrose 


This  abbreviated  table  is  to  be  used  by  means  of  its   ^^  ratios,  which 

are  factors  for  converting  the  reduced  copper  to  its  corresponding  amount 
of  dextrose.  The  most  important  property  of  these  ratios  from  a  practical 
standpoint  is  that  they  change  their  value  slowly  in  comparison  with  the 
amounts  of  reduced  copper  to  which  they  pertain.  For  amounts  of  reduced 
copper  between  48  and  192  mg.  no  table  is  necessary,  as  the  ratios  fluctuate 
about  a  mean  common  factor  of  0.522.  In  all  other  regions  of  the  table  it 
should  be  observed  that  the  slow  change  of  the  ratios  w^ll  enable  the  operator 
to  interpolate  mentally  the  required  ratio  for  any  amount  of  reduced  copper 
lying  between  two  adjacent  values  of  column  ii.  For  the  very  small  amounts 
of  dextrose  the  third  decimal  place  has  no  practical  significance. 

CALORIMETRIC  MEASUREMENTS. 

It  is  a  matter  of  much  regret  and  no  little  chagrin  that  during  the  greater 
part  of  the  time  the  new  experiments  on  diabetics  were  being  carried  out  the 
results  obtained  with  the  bed  calorimeter  were  vitiated  by  some  then  unknown 
factor,  so  that  the  accuracy  of  the  heat  measurement  in  about  two-thirds  of  the 
experiments  is  seriously  questioned.  In  about  one-third  of  the  experiments 
we  know  the  results  to  be  satisfactory  and  accurate,  but  we  have  discarded  all 
of  the  data  rather  than  select  arbitrarily  one-third  of  the  material  for  presen- 
tation. 

The  index  of  this  inaccuracy  is  to  be  found  in  abnormal  relations  between 
the  carbon-dioxide  production,  the  oxj^gen  consumption,  and  the  heat  produc- 


INTRODUCTION.  13 

tion.  As  has  been  pointed  out  in  the  earher  report/  the  relationship  between 
the  oxygen  consumption  and  calories  and  the  carbon-dioxide  production  and 
calories  was  a  relatively  constant  one  for  diabetics,  that  is,  approximately  3.3 
calories  for  every  gram  of  oxygen  consumed  or  carbon  dioxide  produced.  On 
the  completion  of  the  later  experiments  it  was  ascertained  that  these  ratios 
were  abnormally  low,  both  for  oxygen  and  for  carbon  dioxide,  while  the 
respiratory  quotients  as  finally  determined  were  in  full  accordance  with  the 
earlier  work.  A  further  examination  of  the  results,  together  with  a  series  of 
control  experiments,  showed  that  the  apparatus  measured  the  heat  radiated 
from  the  body  most  accurately,  and  the  error  was  finally  found  to  be  in  the 
determination  of  the  water-vapor.  It  was  just  at  this  time  that  fundamental 
alterations  in  the  method  of  determining  the  water-vapor  were  being  intro- 
duced, and  unquestionably  the  errors  in  heat  measurement  can  be  directly 
ascribed  to  this.  Under  these  conditions,  therefore,  we  deem  it  inexpedient  to 
discuss  in  this  report  the  heat  as  measured,  but  as  all  of  the  control  experiments 
point  toward  the  highest  degree  of  accuracy  in  the  measurement  of  the  carbon 
dioxide  and  oxygen,  we  can  confidently  base  our  discussion  upon  these  two 
factors.  Since  in  an  earlier  publication  the  relationships  between  oxygen  con- 
sumption, carbon-dioxide  production,  and  heat  production  were  so  thoroughly 
studied,  and  since  these  well-known  relationships  play  an  important  role  in 
so-called  "indirect  calorimetry,"  the  data  for  the  gaseous  exchange  in  this  new 
series  of  experiments  have  an  increased  significance. 

^Benedict  and  Joslin,  loc.  cit.,  p.  219. 


PART  II. 


STATISTICS  OF  EXPERIMENTS  ON  THE  METABOLISM  OF  DIABETICS. 

These  experiments  were  all  made  with  patients  from  the  private  practice 
of  one  of  us.  Frequently  the  patients  were  placed  in  the  New  England 
Deaconess  Hospital,  within  a  short  distance  of  the  laboratory,  and  the  diet 
strictly  controlled.  Others  lived  in  or  near  Boston  and  made  periodic  visits 
to  the  laboratory  for  experimental  purposes. 

CLASSIFICATION  OF  CASES. 

The  cases  were  divided  into  groups  with  particular  reference  to  severe, 
moderately  severe,  and  light  diabetes.  The  basis  for  this  classification  has 
been  essentially  that  outlined  in  our  previous  publication,  namely,  under  severe 
diabetes  were  classed  all  those  who  failed  to  become  sugar-free,  even  though  all 
carbohydrates  except  the  green  vegetables  were  excluded  from  the  diet,  or 
those  who  became  temporarily  sugar-free  upon  vegetable  days  which  were  fol- 
lowed by  a  low  quantity  of  protein  in  the  diet.     The  cases  in  this  group  invari- 

Table  2. — Description  of  cases  used  in  the  studies  on  diabetes. 


No.  of 
case. 


Desig- 
nation 
of  case. 


Sex. 


Age  at 
onset. 


Onset. 


Present  condition. 


Duration. 


220 
283 
246 
319 
373 
201 


310 
295 
289 
210 
226 
177 
281 
194 
441 
371 
344 

336 
381 
332 
320 
333 
317 


17 
13 
18 
44 
21 
47 
12 
13 
16 
13 
40 

46 
41 
35 
35 
16 
32 


Gradual,  1900 Died,  Aug.  24,  1910 

Gradual,  Dec.  1908 i  Died,  coma,  Apr.  13,  1910 

Acute,  Sept.  1908 {  Died,  coma,  Dec.  8,  1909 

Mar.  1909 Died,  coma,  Jan.  13,  1910 

Sept.  1907 '  Died,  coma,  Oct.  13,  1909 

Jan.  1908 Died,  pneumonia  (?),  Feb.  1910 


yrs.  mos. 
10    .. 


(Transitory  glycosuria,  Jan.  1901; 
final  onset,  Jan.  1905 

1889 

1900 

Feb.  1908 

Nov.  1907 

July  1908 

1900 

July  1909 

Feb.  1908 

Dec.  1910 

Sept.  1909 

Nov.  1903 


Died,  coma,  May  4,  1910. 


1899 

Sept.  1908. 
Apr.  1909.. 
July  1909. . 
Nov.  1908. 
July  1903.. 


Died,  coma,  May  3,  1910 

Died,  May  1912 

Died,  Sept.  17,  1912 

Died,  coma,  Nov.  4,  1910 

Active  work,  Nov.  11,  1912 

Active  work,  Nov.  11,  1912 

Died,  coma,  Feb.  16,  1911 

Died,  coma,  Dec.  10,  1910 

Died,  coma,  Nov.  5,  1911 

Died,  coma.  Mar.  14,  1911 

Died,    pulmonary  tuberculosis, 

Mar.  14,  1912 

Died,  coma,  Oct.  19,  1910 

Died,  coma,  Mar.  5,  1911 

Died,  coma,  Ausic.  H,  1911 

Died,  Feb.  fl,  1911 

Comfortable,  Nov.  11,  1912 

Comfortable,  May  8,  1912 


ably  showed  a  minus  carbohydrate  balance  when  the  diet  was  considerably 
restricted.  The  second  criterion  for  determining  the  severity  of  the  case  was 
the  presence  of  an  acidosis.  Under  moderately  severe  diabetes  were  classed 
those  who  became  sugar-free  and  showed  a  positive  carbohydrate  balance,  or 
with  whom  the  acidosis  was  either  very  slight  or  absent.  Only  one  case  of 
light  diabetes  was  included  in  the  study.     This  was  a  fat  man.  Case  M,  who 

15 


16 


METABOLISM   IN    SEVERE   DIABETES. 


was  able  to  assimilate  at  least  100  grams  of  carbohydrate  per  day.  The  num- 
ber of  cases  of  moderately  severe  and  light  diabetes  are  so  few  as  to  make  them 
a  secondary  consideration  in  this  discussion.  A  brief  description  of  the  cases 
is  given  in  table  2. 

DIET. 

The  diet  of  the  patient  was  arranged  in  accordance  with  that  described 
in  the  previous  report.^  By  strict  diet  is  meant  foods  containing  no  carbo- 
hydrates such  as  meat,  fish,  eggs,  and  their  derivatives,  oil,  butter,  coffee, 
and  tea.  The  vegetables  used  contained  varying  amounts  of  carbohydrates, 
ranging  between  5  and  10  per  cent;  but  the  total  amount  of  carbohydrates 
given  during  the  day  in  the  form  of  cooked  and  uncooked  vegetables  closely 
approximated  and  is  estimated  at  10  grams. 

LIST  OF  EXPERIMENTS  WITH  DIABETICS. 

The  experimental  data  from  which  the  deductions  in  this  book  are  drawn 
were  obtained  from  a  large  number  of  cases  with  a  considerable  number  of 
experiments.  A  list  of  the  experiments  in  the  second  series,  together  with  the 
number  of  periods,  is  given  in  table  3. 


Table 

3. — List 

of  experiments  ivith  diabetics  lying  in 

bed,  1910-1911. 

Calorimeter. 

Respiration  apparatus. 

Without  food. 

With  food. 

Without  food. 

With  food. 

Case. 

No.  of 

No.  of 

No.  of 

^°-  9f   '    No.  of 

No-  9f      No.  of 

experi- 
ments. 

periods. 

experi- 
ments. 

periods. 

experi- 
ments. 

periods. 

=s:     P-ods. 

A 

1 

3 

H 

1 

3 

I 

1 

2 

K 

3 

7 

L 

1 

3 

1 

3 

M 

1 

3 

1 

4 

N 

7 

21 

1 

3 

1 

1 

o 

3 

6 

2 

8 

P 

1 

6 

2 

6 

5 

14 

6 

27 

Q 

2 

6 

2 

6 

R 

1 

2 

3 

4 

s 

i 

3 

1 

4 

T 

2 

4 

U 

2 

6 

1 

4 

4 

10 

7 

31 

V 

1 

5 

W 

2 

7 

X 

Total. . 

13 

>9 

1        j        3 

21 

62 

6 

19 

23 

65 

21 

78 

•  These  experiments  with  Case  X  were  made  with  the  subject  sitting  in  the  chair  calorimeter. 

As  an  indication  of  the  amount  of  experimental  material  available  for 
deductions,  a  summarized  list  of  all  our  experiments  to  date  is  also  given  in 
table  4. 


'Benedict  and  Joslin,  loc.  cit.,  p.  29. 


STATISTICS   OF   EXPERIMENTS. 


17 


Table  4. — Experiments  with  diabetics,  190S-1911. 


1908-1910 
(13  cases). 

1910-1911 
(17  cases). 

1908-1911 
(24  cases).! 

No.  of 
experi- 
ments. 

No.  of 
periods. 

No.  of 
experi- 
ments. 

No.  of 
periods. 

No.  of 
experi- 
ments. 

No.  of 
periods. 

Subjects  sitting  in  chair  calorimeter: 

30 
14 

11 

26 

106 
45 

37 
102 

3 

18 
6 

23 

21 

9 

53 
19 

65 

78 

33 
14 

29 
6 

49 
21 

115 
45 

90 
19 

167 

78 

With  food 

Subjects  lying  in  bed  calorimeter: 

With  food        

Respiration  apparatus  (Ijdng): 

With  food 

>Experiments  with  six  of  these  cases  are  reported  both  in  this  publication  and  in  Publication  No.  136. 

CASE  A. 


DESCRIPTION    OF   THE    CASE. 

Male;  born  May  2,  1860;  single;  traveling  salesman;  developed  diabetes  in 
1900;  came  under  our  observation  in  October  1908;  died  August  24,  1910. 
Full  details  regarding  the  historj^  of  this  case  and  its  treatment  previous  to  1910 
may  be  found  in  an  earlier  publication.^ 

Later  history  of  the  case. — During  the  winter  of  1909-10  the  patient  was  in 
a  comfortable  condition,  and  on  March  1, 1910  felt  quite  well.  He  reported  at 
this  time  that  he  had  been  able  to  work  and  that  his  friends  considered  that  he 
looked  better  than  he  had  for  two  years.  The  quantity  of  urine  varied  from 
2.5  to  3  liters.  His  diet  contained  approximately  60  grams  of  carbohydrate, 
with  8  grams  of  sodium  bicarbonate.  In  June  1910  abscesses  developed  in  the 
right  ear,  and  later  a  furuncle  in  the  occipital  region.  In  the  latter  part  of 
July  there  was  considerable  edema  of  the  right  ankle,  Ijut  this  decreased  when 
the  sodium  bicarbonate  was  discontinued  in  the  early  part  of  August.  In  this 
month  the  diet  was  relaxed  considerably,  the  patient  eating  cantaloupe  and 
watermelon  at  noon  and  peaches  at  night.  Constipation  was  a  troublesome 
symptom,  but  the  strength  was  fairly  good.  A  physical  examination  made 
August  5  showed  a  weight  of  48.6  kilos,  without  clothes;  temperature,  99.1°  F. ; 
blood-pressure,  150;  pulse-rate,  108;  heart  of  normal  size  and  free  from  mur- 
murs; liver  not  enlarged;  pupils  equal  and  reacting  to  light;  knee-jerks  normal; 
moderate  edema  of  the  ankles.  In  the  upper  right  chest  a  few  rales  could  be 
heard  extending  down  to  about  the  fourth  interspace.  There  was  also  a  slight 
cough.  Later,  August  8,  1910,  the  findings  in  the  chest  were  confirmed.  The 
patient  was  last  seen  on  August  22,  1910,  soon  after  his  return  from  a  visit  in 
the  country,  during  which  he  had  suffered  from  gastric  indigestion.  As  a 
result  of  this  he  had  ceased  eating,  omitted  the  sodium  bicarbonate,  and  symp- 
toms of  coma  appeared,  as  was  evident  from  his  report  of  difficult  breathing 
upon  August  20.  He  was  slightly  more  comfortable  on  August  22,  but  air- 
hunger  was  manifest.  At  this  time  the  pulse-rate  was  100,  the  temperature 
normal;  the  acetone  odor  was  absent  from  the  breath.  The  patient  died  on 
August  24,  1910. 

Urine  data. — Only  a  few  observations  were  made  of  the  urine,  and  unfor- 
tunately these  are  not  of  great  significance,  as  the  patient's  diet  was  not  under 

'Benedict  and  Joslin,  Metabolism  in  diabetes  mellitus,  Carnegie  Institution  of  Wash- 
ington Publication  No.  136,  1910,  p.  36. 


18 


METABOLISM   IN    SEVERE    DIABETES. 


control.  August  4-5,  1910,  the  specific  gravity  was  1.024,  with  diacetic  acid 
present,  0.11  per  cent  of  ammonia,  0.36  per  cent  of  nitrogen,  and  2.8  per  cent  of 
sugar  by  copper  reduction  and  2  per  cent  by  rotation.  August  9-10,  1910,  the 
total  amount  of  urine  was  1625  c.c.  with  5.64  grams  of  nitrogen  and  64.3  grams 
of  sugar.  August  10-11,  1910,  the  total  amount  of  urine  was  1380  c.c,  with  a 
slight  trace  of  albumen,  and  3  per  cent  (41  grams)  of  sugar.  Diacetic  acid  was 
also  present.  The  reaction  was  acid  in  all  instances.  The  acidosis  at  this  time 
was  far  less  than  during  most  of  the  year  1909,  and  much  of  October  and 
November  1908.  The  decrease  in  sugar  and  in  ammonia  may  bear  a  relation 
to  the  development  of  active  tuberculosis  in  the  lungs.  Case  R  is,  however,  a 
more  striking  example  of  this  feature. 

EXPERIMENTS   WITH    CASE    A. 

In  the  previous  publication,  16  calorimeter  experiments  were  reported  with 
this  subject.  In  all  but  one  of  these  the  chair  calorimeter  was  used.  The 
only  experiment  with  the  subject  reported  here  is  a  respiration  experiment. 
The  vital  statistics  are  as  follows : 

Date  of  birth.  May  2,  1860;  height,  171  cm.;  body-weight  without  cloth- 
ing during  experiment,  46.1  kilos. 

Respiration  Experiment  No.  A1. 

Date,  August  10,  1910.     Body-weight  without  clothing,  46.1  kilos. 

The  subject  came  to  the  laboratory  the  morning  of  the  experiment,  fasting, 
and  lay  down  upon  the  couch  at  8''  05™  a.  m.  The  experiment  began  at  8''  26™ 
a.  m.,  continuing  for  three  periods,  11  to  15  minutes  in  length,  with  intermis- 
sions of  15  and  20  minutes.  The  experiment  was  without  incident.  The 
results  are  given  in  table  5. 

Table  5. — Results  of  respiration  experiment  No.  Al. 


Date  and  time. 

Carbon 
T-i      ♦•„„     !     dioxide 

per  minute. 

Oxygen 

absorbed 

per  minute. 

Respiratory 
quotient. 

Average 
pulse- 
rate. 

Average 

respiration 

rate. 

Aug.  10,  1910: 
8'»2G'"a.ni 

8  52    a.m 

9  26    a.m 

min.  sec. 
10    47 
1.3    49 
15      7 

c.c. 
136 
133 
131 

c.c. 

'm 

187 

.70 

71 
6S 
68 

13 
13 
13 

1133 

1188 

.71 

69 

13 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.89  c.c;  oyxgen  absorbed  per  kilogram  per  minute,  4.08  c.c. 

CASE  B. 


DESCRIPTION    OF   THE    CASE. 

Female;  born  September  9,  1869;  married;  doing  her  own  housework;  first 
recognized  symptoms  of  diabetes  mellitus  at  the  age  of  39,  December  25, 
1908;  came  under  our  observation  September  1909;  died  in  coma  April  13, 
1910. 

The  earlier  history  of  this  case,  with  the  results  of  experiments  made  with 
her,  has  previously  been  pubhshed.^  No  further  metabolism  experiments 
have  been  made  with  this  subject.  The  patient  gradually  failed  during  the 
spring  of  1910.     Her  weight  on  leaving  the  hospital  March  3,  1910,  was  40.7 

*  Benedict  and  Joslin,  loc.  cit.,  p.  61. 


STATISTICS   OF   EXPERIMENTS. 


19 


kilos.,  without  clothes.  During  the  latter  part  of  March  she  was  troubled  with 
indigestion  for  which  her  physician  gave  calomel,  and  a  sore  mouth  resulted. 
She  continued  to  lose  flesh,  had  considerable  distress  from  food,  with  anorexia 
and  sleepiness.  April  1,  1910,  moderate  jaundice  developed,  and  she  died  in 
coma  upon  April  13,  1910.  Death  was  preceded  by  a  convulsion,  which  was 
followed  by  hemiplegia.     The  urine  was  not  examined  after  March  1,  1910. 

CASE  G. 

DESCRIPTION    OF   THE    CASE. 

Male;  born  December  1874;  married;  broker;  sugar  in  urine,  January  3, 
1901;  came  under  our  observation  February  13,  1909,  but  the  case  had  pre- 
viously been  closely  studied  for  many  years;  died  in  coma  May  4,  1910. 

Full  details  regarding  the  history  of  the  case  and  the  results  of  the  three 
calorimeter  experiments  made  with  him  have  been  given  in  the  earlier  publica- 
tion.^ No  new  experiments  were  made  with  this  subject.  During  the  succes- 
sive 15  months  he  gradually  failed,  despite  an  increase  of  carbohydrates  in  his 
diet  up  to  100  grams  and  large  doses  of  sodium  bicarbonate.  The  urine 
remained  acid  in  reaction  until  death.  Albumen  was  present  on  May  2,  1910. 
The  urinary  record  is  given  in  table  6. 

Table  6. — Clinical  chart — Case  G. 


Date. 

Volume 
of  urine. 

Specific 
gravity. 

Nitrogen. 

Ammonia. 

Sugar  by 

copper 
reduction. 

Carbo- 
hydrates 
in  diet. 

Carbo- 
hydrate 
balance. 

Sodium 

Body 
weight 
without 
clothing. 

Total. 

NHa-N 
Total  N 

bicar- 
bonate. 

1909. 

Apr.  5 

Oct.  23 

1910. 
May  2 

c.c. 
5900 
5190 

6260 

1027 
1027 

1019 

gms. 
18.1 
20.0 

23.8 

gms. 
2.6 
3.4 

5.2 

p.  ct. 
11  8 
14.0 

18.0 

gms. 
183 
151 

157 

gms. 
103 
10± 

gms. 
-80 

gms.         kilos. 
45      1      59.5 
45            58.0 

75              (1) 

'Weight  without  clothing,  Apr.  20,  1910,  53.1  kilos. 


CASE  H. 


DESCRIPTION   OF   THE   CASE. 


Female;  born  May  19,  1872;  single;  nurse;  developed  diabetes  at  17  years 
of  age;  sugar  found  in  urine  at  20  years  of  age;  came  under  our  observation 
January  17,1910;  died  in  coma  May  3,1910.  The  details  of  the  history  of  this 
case  may  be  found  in  the  earlier  publication  previously  referred  to.- 

Later  history  of  the  case. — During  the  spring  of  1910  the  patient  continued 
her  occupation  as  superintendent  of  nurses  of  a  large  out-patient  department 
for  tuberculosis.  Fair  health  and  strength  were  maintained.  On  March  25 
the  patient  had  a  body-weight  of  54.5  kilos.,  and  was  reported  as  being  better 
than  she  had  been  for  years.  On  April  11  an  examination  showed  that  the 
lungs  were  normal,  but  the  patient  was  suffering  from  pains  in  the  legs.  The 
urine  was  pale  in  color,  acid  in  reaction,  and  with  a  very  slight  trace  of  albumen. 
The  urinary  record  is  given  in  table  7. 

The  patient  suddenly  decided  to  go  to  Europe  and  would  not  be  dis- 
suaded. On  the  first  day  out,  as  rough  weather  was  encountered,  she  became 
seasick,  and  for  the  next  three  days  was  unable  to  take  food ;  thereupon  coma 
developed  and  death  ensued  May  3,  1910.  Attention  is  called  to  the  similar 
period  of  starvation  preceding  coma  which  took  place  in  Case  A.     It  would 


^Benedict  and  Joslin,  lor.  cit.  p.  111. 


'Benedict  and  Joslin,  loc.  cit.,  p.  118. 


20 


METABOLISM   IN    SEVERE   DIABETES. 


appear  that  whenever  the  store  of  available  carbohydrates  in  the  body  is 
exhausted,  coma  develops.  For  this  reason  carefully  instructed  diabetic  pa- 
tients are  cautioned  to  guard  against  sudden  inroads  upon  their  scanty  store 
of  glycogen  by  increasing  the  quantity  of  carbohydrates  in  their  diet  whenever 
signs  of  indisposition  appear.  These  patients,  Case  A  and  especially  Case  H, 
knew  this  rule,  but  they  were  unable  to  retain  any  food. 

Table  7. — Clinical  chart — Case  H. 


Date. 

Volume 
of  urine. 

Specific 
gravity. 

Diacetic 
acid. 

Nitrogen. 

Sugar. 

Carbo- 
hydrate 
in  diet. 

By  copper 
reduction. 

By  rota- 
tion. 

1910. 
Mar.  22-23 

c.c. 
3600 
3900 
3420 
2970 

860 

i623 
1024 

+ 
+ 
+ 

gms. 

i5!2 
10.7 
12.6 
2  7 

gms. 

iio 

135 
104 
26 

gms. 
130 
140 
123 

gms. 

'iooi 

24-25" 

Apr.  10-11 

21-22 

222 

lAmmonia,  3.1  gms.; 


NHa-N 
Total  N 


=  16.8  per  cent.;  NaHCOa  taken,  4  to  8  gms. 


2  From  7  a.m.  to  1  p.m. 


EXPERIMENTS    WITH    CASE    H. 

Five  calorimeter  experiments  and  one  respiration  experiment  with  this 
subject  were  reported  in  the  previous  publication.  One  experiment  with  the 
bed  calorimeter  is  reported  here.     The  vital  statistics  were  as  follows : 

Date  of  birth,  May  19,  1872;  height,  159  cm.;  body-weight  without 
clothing  during  experiment,  54.1  kilos. 

Table  8. — Measurements  of  metabolism. — Calorimeter  experiment  No.  HI. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen 
absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 

minute. 

Total. 

Per 

minute. 

Apr.  22,  1910: 

1 9'>  23""  a.m.  to  IQ^  23""  a.m .... 

10  23    a.m.       11    23    a.m.... 

11  23    a.m.       12    29    p.m 

Total,  3  hrs.  6  mins.^. .. 

gms. 
18.6 
20.0 
20.8 

c.c. 
158 
170 
161 

gms. 
17.2 
19.6 
20.3 

c.c. 
201 
228 
215 

0,79 
.74 

.75 

87 
85 
86 

23 
23 
23 

59.4 

163 

57.1 

215 

0.76 

86 

23 

"  Subject  drank  a  cup  of  black  coffee  at  7  a.m. 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.01  c.c;  oxygen  absorbed  per  kilogram  per  minute,  3.97  c.c. 
The  urine  collected  between  7  a.  m.  and  1  p.  m.  amounted  to  860  c.c.  and  contained  2.73  grams  of  nitrogen 
and  25.6  grams  of  sugar.     Sublingual  body -temperature  at  beginning,  98.4°  F.;  at  end  98.2°  F. 

Calorimeter  Experiment  No.  HI. 

Date,  April  22,  1910.     Body-weight  without  clothing,  54.1  kilos. 

On  the  day  of  the  experiment  the  subject  ate  no  breakfast  before  coming 
to  the  laboratory,  taking  only  a  cupful  of  black  coffee  at  7  a.  m.  Her  evening 
meal  the  day  before,  which  was  taken  at  7  o'clock,  consisted  of  shad  with  roe, 
one  French  roll,  and  Romaine  salad  with  French  dressing.  At  10  p.  m.  the 
same  day  she  took  one-half  pint  of  heavy  cream  and  4  ounces  of  wine. 

She  reached  the  laboratory  at  8*^03'°  a.m.,  and  entered  the  bed  calorimeter 
at  8^^  26™  a.  m.  The  experiment  began  at  9''  23"^  a.  m.,  continuing  for  three 
1-hour  periods,  the  last  period  being  extended  6  minutes  in  order  to  secure  favor- 
able temperature  conditions.     The  experiment  ended  at  12^  29""  p.  m.     After 


STATISTICS    OF   EXPERIMENTS. 


21 


the  experiment  the  subject  said  that  throughout  the  whole  experimental  period 
there  was  a  great  pressure  on  the  bladder.  This  doubtless  was  the  cause  of  the 
uneasiness  shown  by  the  subject  as  indicated  by  the  calorimeter  temperature 
fluctuations.  The  measurements  of  the  metabolism  and  data  regarding  the 
pulse  and  respiration  rates  and  urine  are  given  in  table  8. 

CASE  I. 

DESCRIPTION    OF   THE    CASE. 

Male;  born  February  2, 1886;  married;  chauffeur;  date  of  onset  not  known, 
but  probably  some  time  in  1900;  sugar  found  in  urine  May  1902,  with  indica- 
tions that  it  had  been  present  for  some  time;  came  under  our  observation 
October  25,  1909;  died  May  1912.  The  earher  details  of  the  case  have  pre- 
viously been  published  in  full.^ 

An  attack  of  influenza  in  the  spring  of  1910  reduced  the  strength  of  the 
patient  materially,  yet  he  recovered  sufficiently  to  go  into  the  poultry  business 

Table  9. — Clinical  chart — Case  I. 


Ammonia. 

Body- 

Date. 

Volume 
of 

Specific 
gravity. 

Diacetic 
acid. 

3-oxy- 
butyric 

Nitro- 

Sugar 
by  ro- 

Carbo- 
hydrates 

Carbo- 
hydrate 

NaHCOo 

weight 
with- 

urine. 

acid. 

gen. 

Total. 

NHs-N 

tation. 

in  diet. 

balance. 

out 

Total  N 

w 

clothes. 

1911. 

c.c. 

gms. 

gms. 

gms. 

p.  ct. 

gms. 

gms. 

gms. 

gms. 

kilos. 

Feb.  17-18.. 

870  ± 

1035 

0 

'6.4 

18-19.. 

900  ± 

1038 

_}- 

.... 

16.4 

2i5± 

0 

19-20.. 

2220 

1036 

b 

2147 

210 

<+'66 

0 

20-21.. 

1950 

1035 

0 

.... 

2133 

230 

^-1-  95 

0 

21-22. . 

2160 

1035 

S1.+ 

4.5 

i6!e 

i'.h 

12^4 

143 

185 

-f  40 

0 

22-23.. 

2070 

10.35 

S1.+ 

5.9 

11.4 

128 

180 

+  50 

0 

23-24.. 

2555 

103R 

4  8 

13.6 

i.i 

13^3 

164 

175 

+  10 

0 

40 

6 

24-25. . 

1630 

1037 

""  0 

3.8 

8.3 

117 

155 

+  40 

0 

Oct.    2-  3.. 

6000 

1038 

0 

25.8 

ii 

'7;6 

3420 

1912. 

Feb.  9-10.. 

52040 

1036 

0 

139 

175± 

+  35 

12 

39 

4 

10-11.. 

2745 

1032 

++++ 

x.i 

154 

200  ± 

-1-  45 

12 

39 

3 

11-12.. 

31.50 

1030 

li^S 

158 

200  ± 

-1-  40 

12 

12-13.. 

2910 

1028 

-l — 1 — 1 — 1 — j- 

13.4 

116 

200  ± 

+  85 

12 

13-14.. 

2010+ 

1026 

+++++ 

9.6 

\.%^ 

iiii 

76 

200^ 

-M25 

12 

14-15.. 

1320 

200± 

4 

'Per  cent.     -Sugar  by  fermentn.tion,  Feb.  19-20,  151  gms.;  Feb.  20-21,  135  gms.      'By  Fehling's  method,  480  gms. 

'Calculated  from  fermentation  record. 

'  Sediment  showed  fine  and  coarse  granular  casts.     Quantities  of  urine  inaccurate,  as  patient  had  so  manj-  involuntary 

stools. 
'The  data  regarding  the  urine  for  this  subject  can  not  be  considered  reliable,  as  it  was  impossible  to  make  a  careful 

collection,  owing  to  diarrhea.      If  such  collection  had  been  made,  it  is  probable  that  this  subject  would 

have  shown  a  minus  carbohydrate  balance,  as  he  did  in  the  period  covered  by  data  published  in  the  first 

report  (Publication  No.  1.36,  p.  127). 

and  care  for  some  70  hens.  His  diet  was  not  limited  and  included,  among  other 
articles,  2  quarts  of  milk,  6  oranges,  and  10  eggs  daily.  In  February  1911, 
he  returned  to  the  hospital  on  account  of  diarrhea  which  had  existed  for  some 
time.  Under  hospital  care  the  number  of  stools  decreased  from  12  to  5  daily 
and  his  condition  improved.  The  physical  examination  remained  the  same. 
The  patient's  condition  did  not  change  during  1911.  In  the  early  winter 
he  went  to  Tampa,  Florida,  and  found  the  climate  agreeable,  but  in  February 
1912,  as  the  diarrhea  had  returned,  he  again  went  to  the  hospital  for  a  few  daj^s. 
Except  for  emaciation  and  weakness  and  the  presence  of  numerous  furuncles, 
his  condition  had  changed  but  little  since  his  previous  visit  to  the  hospital.  He 
was  much  relieved  by  the  rest  and  soon  returned  home.  In  April  1912  he 
was  considerably  weakened  by  a  carbuncle.  Attention  is  called  to  the  remark- 
able duration  of  this  case,  as  well  as  of  Case  H,  and  to  the  hereditary  history  of 
diabetes  of  each. 


'Benedict  and  Joslin,  he.  cit.,  p.  126. 


22 


METABOLISM   IN    SEVERE   DIABETES. 


The  urinary  record  is  given  in  table  9.  The  records  for  October  1911 
show  probably  a  far  nearer  approach  to  the  patient's  average  urinary  excretion 
than  the  quantities  recorded  in  the  hospital.  During  his  stay  in  the  hospital 
the  amount  of  urine  excreted  was  low,  owing  to  the  diarrhea,  and  possibly 
because  of  restrictions  in  diet,  while  in  October  1911  he  was  absolutely  his 
own  master.  The  low  acidosis  is  notable  and  can  in  a  measure  be  explained  by 
the  liberal  allowance  of  carbohydrates  in  the  diet.  The  reaction  of  the  urine 
was  acid  throughout  the  whole  period  of  observation,  and  there  was  but  a 
slight  trace  of  albumen. 

EXPERIMENTS    WITH    CASE   I. 

Two  experiments  were  reported  with  this  sul^ject  in  the  previous  publica- 
tion; one  additional  experiment  is  reported  here,  for  which  the  bed  calorimeter 
was  used.     The  vital  statistics  for  this  subject  are  as  follows : 

Date  of  birth,  February  2,  1886;  height,  176  cm.;  body-weight  without 
clothing  during  experiment,  40.0  kilos. 

Table  10. — Measurements  of  metabolism — Calorimeter  experiment  No.  I  \. 


Date  and  period. 

Carbon  dioxide 
elimin.ated. 

Oxygen . 
absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 
minute. 

Total. 

Per 
minute. 

Feb.  23,  1911: 

1 9^  32m  a.m.  to  10^  17™  a.m 

10    17    a.m.       11    02     a.m 

Total  1  hr.  30  mins.2 

gms. 
1.5.7 
14.8 

c.c. 
177 
168 

gms. 
15.6 
15.4 

c.c. 
242 
240 

0.73 
.70 

120 
120 

19 
19 

30.5 

173 

31.0 

241 

.72 

120 

19 

'  Subject  drank  a  cup  of  clear  coffee  without  sugar  at  7°  50™  a.m. 

2  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.33  c.c;  oxygen  absorbed  per  kilogram  per  minute,  6.03  c.c. 

Calorimeter  Experiment  No.  Ii. 

Date,  February  23,  1911.     Body-weight  without  clothing,  40.0  kilos. 

Previous  to  this  experiment  the  subject  had  taken  no  food  since  the  even- 
ing meal  of  the  day  before,  with  the  exception  of  a  cupful  of  clear  coffee,  with- 
out sugar,  at  7''  50™  a.  m.  He  arrived  at  the  laboratory  at  8''  05™  a.  m.,  and 
entered  the  bed  calorimeter  in  readiness  for  the  experiment  at  8''  53™  a.  m. 
The  experiment  began  at  9''  32™  a.  m.,  continuing  for  two  45-minute  periods, 

Table  11. — Statistics  of  urine — Calorimeter  experiment  No.  7l. 


Date  and  period. 

Volume. 

Specific 
gravity. 

Total 
nitrogen. 

Sugar. 

Feb.  23,  1911: 

i7''00°'a.m.  to   S'' 15™  a.m 

8    15    a.m.       11    15    a.m 

c.c. 
133 
112 

1.036 
1.037 

gms. 

0.82 

.80 

gms. 
7  8 
6.6 

'Subject  drank  a  cup  of  clear  coffee  at  7^  50™  a.m.,  without  sugar. 

ending  at  11''  02™  a.  m.  The  subject  telephoned  twice  during  the  experiment, 
once  at  the  beginning  of  the  first  period  and  again  in  the  second  period,  at 
lO""  40™  a.  m.,  when  he  asked  how  much  longer  he  would  have  to  stay  in  the 
calorimeter.  Aside  from  this  he  lay  very  quietly.  As  the  chair  calorimeter 
had  been  used  in  the  previous  experiments  with  this  subject,  this  was  his  first 
experience  with  the  bed  calorimeter.  He  said  that  he  did  not  find  the  experi- 
ment especially  irksome,  except  that  lying  still  in  one  position  so  long  made  his 


I 


STATISTICS    OF   EXPERIMENTS. 


23 


back  tired.  The  subject  urinated  at  7  a.  m.  before  coming  to  the  laboratory, 
and  again  at  8^  IS""  a.  m.  He  defecated  at  8''  45"^  a.  m.,  the  feces  being  copious, 
watery,  and  Hght-colored.  Immediately  after  the  experiment  was  over  he 
defecated  again  at  11^  IS"'  a.  m.  No  water  was  taken  during  the  experiment 
The  measurements  of  the  metabolism  and  urine  are  given  in  tables  10  and  11. 

CASE  J. 

DESCRIPTION    OF   THE    CASE. 

Male;  born  March  26,  1889;  single;  no  occupation;  onset  of  diabetes, 
February  1908;  sugar  in  urine  10  days  later;  came  under  our  observation  Sep- 
tember 24,  1909;  died,  September  17,  1912.  The  earlier  history  of  this  case 
has  already  been  published.' 

Later  history  of  the  case. — No  experiments  have  been  made  with  this  sub- 
ject other  than  those  previously  published.  From  February  23,  1910,  until 
August  25,  1910,  inclusive,  the  patient  remained  comfortable.  Upon  two 
occasions  the  effect  of  oatmeal  was  tried.  In  the  first  trial,  July  20-23,  1910, 
inclusive,  the  initial  day  was  a  vegetable  day ;  upon  the  two  subsequent  days 
180  grams  of  carbohydrates  were  given  each  day  in  the  form  of  oatmeal.  A 
positive  carbohydrate  balance  of  55  and  40  grams  respectively  was  obtained  in 
contrast  with  a  positive  carbohydrate  balance  of  5  grams  upon  the  vegetable 


Table  12 

.- 

—Clinic 

d  chart — 

Case  J. 

6 

>i 

Ammon 

a.       Sugar. 

Diet. 

"5 

J3 

c 

'> 

2 

Is 

1 

—   2 

13 

oj 

L., 

a 

' 

S  • 

-C.I5 

Date. 

"o 

41 

s 

_3 

o 

'3 

a 

§ 
1 

"3 

1 

talN 

coppe 
duction, 

,0 

>> 

B 
'S 

c 

b' 

0) 

0 
0 

! 

>.  B 

.a  a 

.sp-g 

■V  0 

"o 

Q« 

0 

0      >)  g 

>1 

c3  t3 

t; 

■5 

CS 

0 

> 

OS 

0 

iS 

H 

2; 

H     fQ  ^ 

ca 

0 

CL, 

s 

fe 

<: 

c 

0 

« 

1910. 

c.c. 

gms. 

gms.  J 

9. 

ct.    gms. 

gms. 

gms. 

gms. 

gms. 

gms. 

gms. 

gms. 

kilos. 

Mar.  17-18. . 

2820 

1025 

+ 

19.1 

42 

56 

16 

.      -25 

27-28.. 

3240 

10.1 

33 

28-29.. 

3240 

loie" 

"+'+ 

z.h 

-t- 

ig 

"is' 

Aor.  15-16... 

2160 

1022 

0 

-1- 

43 

21 

5ii 

May  29-30.. 

1800 

1031 

SI.+ 

-h 

40 

30 

54.5 

July  1-2.... 

1800 

1033 

+ 

50 

20 

54.0 

20-211  2. 

2370 

1020 

++ 

zi 

.      ...^ 

14 

18 

h 

"2 

'12 

'.      +5 

54.0 

21-22'  3. 

2640 

1023 

0 

"5:3 

125 

106 

180 

43 

5 

iu 

12 

22- 

2     -1-55 

54,5 

22-23  >  3. 

2910 

1034 

S1.+ 

7.3 

142 

122 

180 

43 

5 

144 

12 

22" 

2     -1-40 

54.5 

Aug.  22-23'  \ 

1980 

1023 

++ 

9.6 

3.2     i 

7 

4        32 

20 

35 

12 

2 

160  ± 

12 

17 

2-1-5 

23-24' K 

2490 

1027 

++ 

6.2 

1.7     '. 

>2 

6       111 

95 

180 

43 

7 

170± 

12 

25( 

6     -1-70 

54^6 

24-25'  8. 

1590 

1027 

+++ 

8.8 

1.1 

0 

3         28 

16 

40 

90 

15 

170± 

6 

20f 

2     -f-10 

54.5 

'8  grams  of  sodium  bicarbonate  given.  ^  Vegetable  day. 

'Oatmeal  day,  270  gms.  oatmeal,  180  gms.  butter,  beef  tea,  120  gms.  wine. 

*750  gms.  5  per  cent.-|-6  per  cent  vegetables,  375  c.c.  cream,  105  gms.  butter,  oil,  beef  e.xtract,  120  gms.  wine. 
'270  gms.  oatmeal,  ISO  gms.  butter,  125  c.c.  cream,  beef  e.xtract,  120  gms.  wine.     Feeling  quite  well. 
'2eggs,  bacon,  630 gms.  vegetables  5,  6,  10  per  cent,  60  gms.  pineapple,  300  gms.  meat,  30  gms.  oil,  375  c.c. 
cream,  90  gms.  butter,  60  gms.  wine. 

day.  The  second  experiment  was  made  August  22-25,  1910,  inclusive.  The 
first  day  was  a  vegetable  day  with  375  c.c.  of  cream;  the  second  day  an  oatmeal 
day  in  which  180  grams  of  carbohydrate  were  taken  in  the  form  of  oatmeal; 
on  the  third  day  approximately  40  grams  of  carbohydrate,  90  grams  of  pro- 
tein, 6  grams  of  alcohol,  and  170  grams  of  fat  were  eaten.  The  oatmeal  pro- 
duced a  positive  carbohydrate  balance  of  70  grams.  Upon  the  vegetable  day 
preceding  the  oatmeal  day  the  carbohydrate  balance  was  10  grams.  The 
urinary  record  for  this  case  is  given  in  table  12.  The  reaction  for  the  urine  was 
acid  throughout.  On  April  IG  and  in  the  July  observations  the  slightest  pos- 
sible trace  of  albumen  was  found.  In  the  August  observations,  however,  this 
had  disappeared. 


1  Benedict  and  Joslin,  loc.  cil.,  p.  131. 


24 


METABOLISM   IN    SEVERE   DIABETES. 


CASE  K. 
DESCRIPTION    OF   THE    CASE. 

Male;  born  June  1863;  widower;  undertaker;  onset  of  diabetes,  November 
1907;  came  under  our  observation  August  19,  1908;  died  in  coma  November  4, 
1910.     The  early  history  of  the  case  has  previously  been  published.^ 

On  February  24,  1910,  the  patient  reported  himself  as  feeling  very  well. 
The  quantity  of  urine  was  said  to  be  2000  c.c. 

On  March  26,  1910,  he  said  that  his  face  felt  alternately  flushed  or  numb, 
and  he  suffered  from  both  polyphagia  and  polydipsia.  Although  on  the  day 
previous  he  had  had  diarrhea,  he  was  constipated  on  this  day.  He  was  just 
recovering  from  an  attack  of  the  grippe,  from  which  he  had  been  suffering  six 
weeks.  A  physical  examination  on  this  date  gave  the  following  results :  Lungs 
normal;  heart,  both  first  and  second  sounds  at  the  left  border  of  the  sternum 
prolonged;  blood-pressure,  115;  pulse-rate,  84. 

In  July  1910,  he  again  entered  the  hospital.  There  appeared  to  be  no 
particular  change  in  his  condition,  except  a  loss  in  weight.  His  diet  had  been 
lax,  and  he  said  that  he  felt  better  than  when  on  a  strict  diet.  On  November  4, 
1910,  the  patient  died,  having  been  in  coma  for  about  28  hours.  Except  for 
complaints  of  headache  during  the  previous  week,  no  especial  change  had  been 
noted  in  his  condition. 

The  data  regarding  the  urine  from  March  22  to  August  24,  1910,  inclusive, 
are  given  in  table  13.  At  the  times  of  these  observations  the  urine  gave  an 
acid  reaction.     Very  sUght  traces  of  albumen  were  found  from  July  24  to  28, 

but  none  later. 

Table  13. — Clinical  chart — Case  K. 


>> 

■z 
1 

Ammonia. 

Sugar. 

.5 

a 
a 
"o 

8 

03 

Date. 

6 

e 

3 

> 

2 

u 

U3 

1 
1 

> 

> 

o 

I 

+3 

1 

ip 

li 

D.S 
O  O 
U  3 

•a 

a 

1 
o 

>> 

ii 

0 

0 

0 

> 

P 

<i 

L             S 

H 

zlH 

P3  "• 

03 

o 

< 

0 

'A 

CQ 

1910. 

C.C. 

gm 

s.    gms. 

gms. 

p.  ct. 

gms. 

gms. 

gms. 

gms. 

gms. 

gms. 

kilos. 

Mar.  22-23 

2750 

1033 

Sl.-h 

138 

Mar.  25-26 

2750 

1031 

S1.+ 

116 

July  24-25 

4500 

1029 

0 

.     25.3 

m     180 

0 

July  25-26' 

2920 

1031 

+ 

.      12.0 

186  12  175 

0 

July  26-27 

2550 

1031 

++ 

.     14.8 

4 

9 

27.2 

142  (  122 

60 

12 

-  80 

0 

July  27-28 

2440 

1031 

+-I- 

.     16.0 

5 

8 

29.8 

128  !    98 

50 

12 

-  80 

12 

Julv  28-29 

3030 

1030 

++++ 

.      15.6 

175 

152 

50 

12 

-125 

12 

July  2&-30 

4560 

.     20  1 

197 

55 

18 

-140 

20 

July  30-31 

4560 

.     24.0 

188 

50 

18 

-140 

20 

56.1 

Julv  31-Aug.  1.... 

3600 

1026 

+++ 

.      17.6 

122 

ii5 

40 

18 

-  80 

20 

55.6 

Aug.  1-2 

5580 
4400 
5000 

1030 
1028 
1030 

++ 

30 

22 

.      17.7 
3     17.6 
0     23.1 

3 

4 

\5.9 

268 
188 
245 

185 

240 

55 
50 

18 
18 

-215 
-140 

20 
20 

55!  6 

Aug.  2-3 

Aug.  23-24 

'For  19  hrs.,  from  12  noon  July  25  to  7  a.m.  July  26. 


^By  fermentation  method,  178  gms. 


EXPERIMENTS   WITH    CASE    K. 

One  calorimeter  experiment  and  one  respiration  experiment  with  this  sub- 
ject were  reported  in  the  previous  publication.  These  were  both  fasting  exper- 
iments, the  chair  calorimeter  being  used  in  the  calorimeter  experiment.  In 
this  publication  three  respiration  experiments  are  reported.  The  vital  statis- 
tics are  as  follows: 

Date  of  birth,  June  1863;  height,  180  cm.;  body- weight  without  clothing 
during  experiments,  55.6  kilos. 


^Benedict  and  Joslin,  loc.  cit.,  p.  139. 


STATISTICS    OF   EXPERIMENTS. 


25 


Respiration  Experiment  No.  K1. 

Date  July  27,  1910.     Body-weight  without  clothing,  55.6  kilos. 

The  subject  came  to  the  laboratory  fasting,  having  had  no  food  since  the 
evening  meal  of  the  day  before.  The  experiment  included  but  one  period  of 
approximately  15  minutes,  beginning  at  1^  24"^  a.  m.  This  period  was  without 
incident,  the  subject  remaining  very  quiet.  The  results  of  the  experiment 
may  be  found  in  table  14. 

Respiration  Experiment  No.  K2. 

Date,  July  29,  1910.     Body-weight  without  clothing,  55.6  kilos. 

On  the  morning  of  the  experiment,  the  subject  came  to  the  laboratory 
without  breakfast  and  lay  down  upon  the  couch  at  8^  20™  a.  m.,  and  the  experi- 
ment began  at  8*^34™  a.  m.,  continuing  for  three  periods  of  11  to  14  minutes, 
with  intermissions  of  8  to  10  minutes.  During  the  first  period  the  subject 
cleared  his  throat  once,  and  there  was  probably  a  slight  loss  of  air.  In  the 
second  period  he  moved  his  hands  several  times  and  his  leg  once.  In  the  third 
period  he  lay  quietly  the  whole  time.  The  results  of  the  experiment  are  given 
in  table  14. 

Respiration  Experiment  No.  K3. 

Date,  August  2,  1910.     Body-weight  without  clothing,  55.6  kilos. 

The  subject  came  to  the  laboratory  without  breakfast  at  1^  30"^  a.  m.  and 
lay  down  on  the  couch  at  1^  35™  a.  m.  The  experiment  began  at  7*"  50™  a.  m., 
and  continued  for  three  periods  of  13  to  15  minutes  each,  with  intermissions  of 
8  to  13  minutes,  ending  at  8''  54™  a.  m.  After  the  close  of  the  second  period  the 
pneumograph  was  loosened,  as  the  subject  complained  it  was  too  tight.  Before 
the  beginning  of  the  third  period  the  subject  raised  both  legs  up  at  the  knee, 
and  near  the  end  of  this  period  he  straightened  out  one  leg.  The  results  of  the 
experiment  are  given  in  table  14. 

Table  14. — Results  of  respiration  experiments  Nos.  K1-K3. 


Experi- 
ment 
No. 

Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratorj- 
quotient. 

Average 
pulse  rate. 

Average 

respiration 

rate. 

Kl 
K2 

K3 

Julv  27,  1910: 

7''24'"a.m 

min.  sec. 
15    41 

11      4 
10    58 
14    19 

c.c. 
'182 

c.c. 
1257 

0.71 

77 

18 

July  29,  1910: 

8''34™a.m 

179 
187 
183 

'249 
258 

';75 
.71 

74 
75 
75 

19 
18 
IS 

10    14    a.m 

Average 

2  183 

S254 

.73 

75 

18 

Aug.  2,  1910: 

T*"  50™  a.m 

12    37 
14    37 
14    43 

189 
184 
188 

267 
259 
269 

.71 

.71 
.70 

79 
83 
81 

19 
20 
19 

8    11    a.m 

8    39    a.m 

'187 

3  265 

.71 

81 

19 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.27  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.62  c.c. 
-Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.29  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.57  c.c. 
' Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.36  c.c. ;  oxygen  absorbed  per  Idlogram  per  minute,  4.77  c.c. 

CASE  L. 
DESCRIPTION    OF    THE    CASE. 

Male;  born  October  18, 1886;  single;  student;  onset  of  diabetes  July  1908; 
diagnosed  as  diabetes  on  December  9, 1908;  came  under  our  observation  Decem- 
ber 15,  1908;  condition,  November  11,  1912,  active  work.  The  earher  details 
of  this  case  have  already  been  published.^ 

'Benedict  and  Joslin,  lac.  cit.,  p.  144. 


26 


METABOLISM   IN    SEVERE    DIABETES. 


Between  February  24, 1910,  and  September  28, 1910,  the  patient  remained 
in  excellent  condition,  and  apparently  free  from  sugar  most  of  the  time. 
Although  sugar  was  present  in  the  urine  upon  April  19,  1911,  it  disappeared  in 
three  days  with  the  limitation  of  the  carbohydrates  to  25  grams.  A  physical 
examination  on  this  date  showed  that  the  blood-pressure  (Riva-Rocci)  was  100, 
and  that  there  was  a  slight  systolic  murmur  at  the  apex  of  the  heart  which  was 
just  within  the  mammillary  line.  The  liver  extended  one  finger's  breadth  below 
the  costal  margin.  These  findings  were  confirmed  on  October  12,  1911.  The 
patient  is  now  (May  1912)  doing  active  work. 

The  urinary  record  is  given  in  table  15.  The  reaction  of  the  urine  was 
acid  throughout;  there  was  no  albumen  present  except  a  very  slight  trace  on 
April  21-22,  1911.  The  last  sample  of  urine  received  from  this  subject  was 
on  May  31,  1912;  the  reaction  was  acid,  and  there  was  neither  albumen  nor 
sugar.  On  September  21-22,  1910,  it  wiU  be  seen  that  there  were  20  grams  of 
sugar  in  the  urine;  on  this  day  he  did  an  unusual  amount  of  physical  work. 

Table  15. — Clinical  chart — Case  L. 


Date. 

Volume 
of  urine. 

Specific 
gravity. 

Diacetic 
acid. 

Nitro- 
gen. 

Sugar. 

Carbo- 
hydrates 
in  diet.i 

Carbo- 
hydrate 
balance. 

Body 
weight 
without 
clothing. 

By  copper 

By 

reduction. 

rotation. 

1910. 

c.c. 

gins. 

gtns. 

gms. 

gms. 

gms. 

kilos. 

Sept. 21-22 

1875 

1028 

Sl.-t- 

26.4 

20 

8 

45 

+25 

67.7 

25-26 

1750 

1022 

24.6 

6 

27-28 

21500 

si.+ 

0 

45 

+45 

66  5 

1911. 

April  18-19 

1625 

1030 

+ 

13 

45 

-1-30 

65.6 

21-22 

1375 

1029 

0 

26.6 

0 

25 

+25 

Oct.    11-12 

1625 

1032 

S1.+ 

20.2 

37.5 

26 

30 

-  5 

65  1 

1912. 

May    30-31 

1750 

1022 

0 

'  No  sodium  bicarbonate  given. 

=  From  7'»30™a.m.  to  10*^  10"  a.m.,  Sept.  27,  1910,  volume  of  urine,  434  c.c;  specific  gravity,  1.016;  nitrogen, 
2.72  gms.;  sugar,  3.7  gms.  Another  specimen  of  urine  on  Sept.  28,  1910,  with  a  specific  gravity  of  1.022  gave 
an  acid  reaction,  showed  no  albumen  or  .sugar,  and  only  a  slight  trace  of  diacetic  acid. 


EXPERIMENTS   "WITH    CASE   L. 

In  the  preceding  publication  five  calorimeter  experiments  with  this  sub- 
ject were  reported.  In  four  of  these  the  chair  calorimeter  was  used, the  other 
being  Avith  the  bed  calorimeter.  Two  additional  experiments  are  reported 
here,  both  respiration  experiments.     The  vital  statistics  are  as  follows: 

Date  of  birth,  October  18,  1886;  height,  183  cm.;  body-weight  without 
clothing  during  experiments,  66.5  kilos. 

Respiration  Experiment  No.  LI. 

Date,  September  26, 1910.     Body-weight  without  clothing,  66.5  kilos. 

The  subject  came  to  the  laboratory  at  7''  55°^  a.  m.  fasting  and  imme- 
diately lay  down  upon  the  couch  after  the  pneumograph  and  stethoscope  had 
been  adjusted.  As  the  subject  was  quite  confident  that  he  would  be  able  to 
stay  awake  and  keep  his  mouth  firmly  closed,  surgeon's  plaster  was  not  used 
over  the  mouth  in  the  first  period.  As  the  results  indicated  that  there  might 
be  a  leakage  through  the  mouth,  the  plaster  was  used  in  the  last  two  periods. 
The  experiment  began  at  9''  12^"  a.  m.,  and  continued  for  three  periods  of  13  to 
15  minutes,  with  intermissions  of  10  and  12  minutes,  ending  at  10''  14™  a.  m. 
The  subject  moved  his  hands  and  arms  occasionally,  and  changed  his  position 
slightly,  once  putting  his  hand  to  his  face.     Although  just  previous  to  the 


STATISTICS    OF   EXPERIMENTS. 


27 


third  period  he  said  that  he  was  not  at  all  tired  and  was  willing  to  continue 
indefinitely,  there  was  more  movement  than  in  the  previous  periods.  The  sub- 
ject breathed  very  deeply,  which  was  probably  due  to  the  fact  that  he  had  been 
active  in  athletics  while  in  college  and  had  also  sung  a  great  deal.  He  was 
considered  an  extremely  good  subject,  as  he  was  quiet  and  cooperated  intelli- 
gently.    The  results  of  the  experiment  are  given  in  table  16. 

Table  16. — Results  of  respiration  experiment  No.  LI. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

Sept.  26, 1910: 

9'»12">a.m 

9    30    a.m 

min.  sec. 
15     17 
12    60 
12    48 

c.c. 
205 
207 
204 

c.c. 
281 

278 
285 

0.73 

.74 
.72 

69 
70 
66 

8 
9 
7 

10    01    a.m 

1205 

1281 

.73 

68 

8 

1  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.08  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.23  c.c. 
Respiration  Experiment  No.  L2. 

Date,  September  27,  1910;  body-weight  without  clothing,  66.5  kilos. 

After  a  breakfast  at  7''  4-5"'  a.  m.,  consisting  of  36  gms.  oatmeal  (weighed 
dry),  1.5  ounces  of  butter,  2  boiled  eggs,  a  cupful  of  coffee,  and  half  of  a  grape- 
fruit, the  subject  came  to  the  laboratory  at  8'' 35™  a.  m.  He  lay  down  upon 
the  couch  at  8''  38™  a.  m.,  and  the  experiment  began  at  8''  48™  a.  m.  The  three 
15-minute  periods,  with  intermissions  of  14  to  18  minutes,  ended  at  10'' 05™  a.m. 
Surgeon's  plaster  was  used  to  secure  perfect  closure  of  the  mouth.  After  the 
experiment  the  subject  urinated  at  10''  10™  a.m.  The  results  of  the  experiment 
may  be  found  in  table  17. 

Table  17. — Results  of  respiration  experiment  No.  L2. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse  rate. 

Average 

respiration 

rate. 

Sept.  27,  1910: 

i8'>48'°a.m 

9    21    a.m 

9   50    a.m 

min.  sec. 
15      6 
15     11 
15     12 

c.c. 
241 
247 

268 

c.c. 
329 
337 
336 

0.73 
.73 

.80 

75 
70 
65 

7 
7 
7 

2  252 

2  334 

.75 

70 

7 

1  Subject  ate  breakfast  at  7''  45™  a.m. 

2 Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.79  e.c:  oxygen  absorbed  per  kilogram  per 
minute,  5.02  c.c.  The  urine  collected  between  7°  30™  a.  m.  and  lO''  10"  a.m.  amounted  to 
434  c.c,  specific  gravity  1.016,  and  contained  2.72  grams  of  nitrogen  and  3.7  grams  of  sugar. 

CASE  M. 

DESCRIPTION   OF   THE   CASE. 

Male;  born  January  23,  1853;  married;  dentist;  sugar  found  in  urine  in 
1900;  came  under  our  observation  January  6,  1908;  condition  November  11, 
1912,  active  work.  The  earher  details  of  this  case  have  been  pubhshed  in  a 
previous  publication.^ 

Later  history  of  the  case. — During  the  winter  of  1909  and  1910  the  patient 
insists  that  he  did  more  work  than  he  ever  did  in  his  life  before,  working  even 
Sundays  and  until  11  o'clock  at  night.     He  used  oil  freely,  often  putting  it  on 

^Benedict  and  Joslin,  loc.  cit.,  p.  152. 


28 


METABOLISM    IN    SEVERE    DIABETES. 


strawberries,  oranges,  and  grapefruit,  and  even  used  it  on  bananas,  apples,  and 
cantaloupe.  A  physical  examination  July  5,  1910,  showed  the  blood-pressure 
to  be  120;  pulse-rate,  96;  heart  5  cm.  to  the  right  of  the  median  line,  the  left 
border  lying  within  the  mammillary  line,  with  systolic  murmur  at  the  left 
border  of  the  sternum  and  at  the  base.  The  liver  was  2  to  3  fingers'  breadth 
below  the  costal  margin.  The  spleen  was  not  palpated.  On  November  28, 
1910,  the  weight  v/as  82.6  kilos.,  the  pulse-rate  84,  and  the  condition  good, 
except  for  pain  in  the  vicinity  of  the  sixth  rib  near  the  mammillary  line.  This 
pain  resulted  from  a  fall  and  a  possible  fracture  of  the  rib.  On  December  16, 
1910,  he  was  considerably  shaken  up  in  a  railroad  accident,  besides  being 
exposed  to  a  nervous  strain  in  escaping  from  an  overturned  car.  It  will  be 
seen  from  table  18,  which  gives  the  urinary  record,  that  the  quantity  of  sugar 
in  the  urine  increased  at  this  time.  In  May  1911  he  took  a  5  weeks'  vacation 
trip  to  Europe.  A  physical  examination  gave  the  same  results  as  previously. 
On  October  3,  1911,  the  patient  had  symptoms  suggesting  an  attack  of  biliary 
colic.  These  subsided  gradually,  however,  and  after  a  week's  rest  recovery 
was  complete.  On  December  28,  1911,  his  condition  was  excellent.  An 
examination  showed  that  no  murmur  could  be  heard  in  the  heart.  The  blood- 
pressure  was  125  and  the  pulse-rate  88.  There  was  a  slight  resistance,  but  no 
tenderness  in  the  region  of  the  gall-bladder.  In  the  observations  made  of  the 
urine  an  acid  reaction  was  shown  throughout ;  there  was  a  slight  trace  of  albu- 
men on  January  1,  1911,  and  a  very  slight  trace  on  May  15,  October  2,  and 
December  23. 

Table  18. — Clinical  chart — Case  M. 


Date. 


1910. 
June30-July  1. 

July  14-1.5 

Oct.  1-2 

1911. 
Dec.  31-Jan.  1' 
May  15-16.  ... 
Aug.  27-28.... 

Oct.  1-2 

Oct.  3-4 

Dec.  22-23 


Volume 

Specific 

of  urine. 

gravity. 

c.c. 

1340 

1028 

940 

1029 

890 

1027 

1450 

1030 

975 

1028 

750 

1024 

1200 

1024 

1025 

950 

1027 

Diacetic 
acid. 


Sugar. 


Nitrogen.  ! 


By  copper 
reduction. 


0 

+ 
+ 

+ 
Si.  + 
0 
0 
0 
0 


gms. 


15.5 
13.4 
10.4 


gms. 
14 


By  rota- 
tion. 


gms. 
19 
6 
0 

26 


5 

=  0.2 

3 


Body- 
weight 
without 
clothing. 


hilos. 


81.7 


80.6 


NHs— N 
'j8-oxybutyricacid,  1.9  gms.;  ammonia,  1.3  gms.;  _,      .  „  =6.9  per  cent.;  sugar  by  fermentation,  36  gms. 

2Per  cent. 

EXPERIMENTS   WITH    CASE    M. 

Three  calorimeter  experiments  wdth  this  subject  were  reported  in  the  pre- 
vious publication.  In  two  of  the  experiments  the  bed  calorimeter  was  used; 
the  chair  calorimeter  was  used  in  the  third.  Two  additional  experiments  are 
reported  here,  one  with  the  bed  calorimeter  and  one  with  the  respiration  appa- 
ratus.    The  vital  statistics  are  as  follows: 

Date  of  birth,  January  23,  1853;  height,  172  cm.;  range  in  bodj-weight 
without  clothing  during  experiments,  81.7  to  82.9  kilos. 
Respiration  Experiment  No.  Ml. 

Date,  August  17,  1910.     Body-weight  without  clothing,  81.7  kilos. 
This  experiment,  which  was  made  with  the  respiration  apparatus  and  with 
the  subject  fasting,  included  four  separate  periods  of  10  to  11  minutes  each, 


STATISTICS   OF    EXPERIMENTS. 


29 


with  intermissions  ranging  from  11  to  19  minutes.  The  experiment  began  at 
S^  13™  a.  m.,  and  ended  at  9''  39™  a.  m.  The  subject  was  instructed  not  to  go 
to  sleep  and  apparently  did  not;  in  the  second  period  he  was  uneasy,  moving  his 
legs  and  changing  his  position  somewhat  several  times.  In  the  third  period 
the  observer  thought  the  subject  opened  his  mouth  and  moistened  his  lips,  but 
he  himself  thought  he  did  not.     The  results  of  the  experiment  are  given  in 

table  19. 

Table  19. — Results  of  respiration  experiment  No.  Ml. 


Date  and  time. 

Carbon 
per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

Aug.  17.  1910: 

8'' 13"' a.m 

8  43    a.m 

9  08    a.m 

9    29    a.m 

Average 

min.  sec.              c.c. 

10  50                197 

11  10      1          200 
10      9                187 
10    25      !          203 

c.c. 

271 
256 

260 

6'74 
.73 

.78 

76 
76 
74 
"74 

9 
9 
10 
9 

2197                =262                  .75        j          75          |            9 

'  One  record  of  pulse. 

2  Carbon  dioxide  eliminated  per  kgm.  per  minute,  2.41  c.c.;  oxygen  absorbed  per  kgm.  per  minute, 

3.21  c.c.    The  100c. c.  of  urinecollected  between  6    4.5™ a.m.  and  9h45™a.m.  contained  1.56gm. 

nitrogen  and  1  gm.  sugar. 

Calorimeter  Experiment  M2. 

Date,  June  15,  1911.     Body-weight  without  clothing,  82.9  kilos. 

The  subject  came  to  the  laboratory  without  breakfast  at  7^25"  a.  m., 
entered  the  bed  calorimeter  at  7^56™  a.m.,  and  the  experiment  began  at  8''52"' 
a.  m.  Three  periods,  one  of  53  minutes  and  two  of  45  minutes,  were  included 
in  this  experiment.  Except  in  the  second  period,  when  he  rolled  over  on  his 
side  and  used  his  arms  considerably  in  handling  the  newspaper  he  was  reading, 
the  subject  was  very  quiet  all  through  the  experiment.  Afterwards  he  said  he 
was  very  comfortable  while  in  the  apparatus  and  suffered  no  discomfort.  The 
metabolism  measurements  are  given  in  table  20. 

Table  20. — Measurements  of  metabolism — Calorimeter  experiment  No.  M2. 


Date  and  period. 

'''^^^^^'     1  Oxygen  absorbed. 

Respira- 
tory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 
minute. 

Total. 

Per 
minute. 

June  15.  1911: 

S*"  52""  a.m.  to    9^  45"*  a.m 

9    45    a.m.       10    30    a.m 

10    30    a.m.       11    15    a.m 

gms.              c.c. 
19.7      !        190 
16.6              189 
17.0      ,        192 

gms. 
18.0 
15.7 
15.9 

c.c. 
239 
244 

248 

0.79 
.77 
.78 

70 
68 
67 

11 

Total  2  hrs.   23  min.' 

53.3      1        190 

1 

49.6             243      :        .78             68 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.29  c.c:  oxygen  absorbed  per  kilogram  per  minute,  2.93 c.c. 
The  urine  collected  between  about  lO''  30™  p.m.  June  14  and  12*^  15'"  p.m.  June  15,  specific  gravity  1.025,  amounted 
to  335  c.c.  and  contained  4.12  gms.  of  nitrogen  and  3.6  gms.  of  sugar. 


CASE  N. 
DESCRIPTION   OF   THE    CASE. 

Male;  born  August  1,  1896;  developed  diabetes  just  before  13  years  of  age 
in  July  1909,  and  came  under  our  observation  August  1909;  died  in  coma  Feb- 
ruary 16,  1911. 

Family  history. — Grandmother  died  of  diabetes  at  the  age  of  78.  The 
patient  was  an  only  child,  and  his  father  and  mother  are  well. 

Past  history. — Measles. 


30  METABOLISM   IN    SEVERE   DIABETES. 

Present  illness. — Early  in  June  1909  the  boy  began  losing  weight  while 
riding  a  new  bicycle.  During  the  first  part  of  August,  frequent  micturition 
developed  and  in  the  course  of  a  few  days  he  began  to  droop. 

Physical  examination. — Height,  146  cm.;  greatest  weight,  34.5  kilos.; 
weight  August  28,  1909,  29.6  kilos.  Fairly  well  developed.  Pupils  equal  and 
reacted  to  light.  Tongue  and  teeth  normal.  Lungs  normal.  Heart  extended 
2  cm.  to  right  of  median  line  and  9  cm.  to  left  of  median  line  (just  external  to 
mammillary  line).  Systolic  murmur  at  apex.  The  liver  extended  2  fingers' 
breadth  below  the  costal  margin.     Knee-jerks  normal.     No  edema. 

Urine  data. — The  greatest  quantity  of  urine  observed  was  at  the  onset, 
when  it  reached  3500  c.c.  The  patient's  urine  contained  6.6  per  cent  of  sugar 
on  August  28  and,  on  the  following  day,  162  grams  were  excreted.  By  the 
restriction  of  the  diet  to  20  grams  carbohydrate,  the  urine  became  sugar-free 
on  September  13  and  this  condition  was  maintained  almost  constantly  until 
November  22,  1909;  he  then  evidently  broke  diet  and  the  sugar  in  the  urine 
went  up  to  7  per  cent  (88  grams). 

The  sugar  did  not  again  disappear  from  the  urine  until  December  15, 
when  the  patient  was  at  the  hospital.  It  remained  absent  for  the  4  days  he 
was  there,  returning  promptly  when  he  left  the  institution,  and  never  disap- 
peared save  upon  two  days  in  January  and  one  in  February  of  the  following 
year. 

Albumen  was  either  absent  or  present  only  in  extremely  small  quantities; 
during  the  last  few  months  of  life  but  a  trace  was  present. 

The  urine  was  invariably  acid,  save  upon  one  day,  December  18,  1909. 
During  the  first  period  of  observation,  from  August  1909  until  April  1910,  the 
signs  of  acidosis  were  slight  and  represented  at  the  most  by  only  a  moderate 
reaction  for  diacetic  acid.  From  that  time  on  they  increased,  and  the  acidosis 
was  extreme  in  November  1910,  when  the  patient  was  again  in  the  hospital. 
At  this  time  the  urinarj^  record  (table  21)  shows  35  grams  of  jS-oxybutyric  acid 
in  one  day,  and  on  the  same  day  4.2  grams  of  ammonia. 

Death  finally  occurred  on  February  16,  1911,  after  3  days  of  coma.  The 
case  therefore  affords  a  most  excellent  example  for  a  study  of  diabetes  with  and 
without  acidosis.  During  its  duration  of  19  months,  the  disease  ran  a  course 
free  from  complication,  with  the  exception  of  the  persistent  ulceration  of  one 
incisor  tooth. 

EXPERIMENTS   WITH    CASE   N. 

Yv'ith  this  subject,  eight  calorimeter  experiments  were  made,  in  all  of  which 
the  bed  calorimeter  was  used.  In  seven  experiments  the  subject  entered  the 
apparatus  without  breakfast,  after  a  12  hours'  fast.  One  experiment  was 
made  following  a  breakfast  of  cooked  oatmeal.  In  addition,  one  respiration 
experiment  was  carried  out  with  this  subject.  The  data  for  the  calorimeter 
experiments  are  compared  in  table  33.     The  vital  statistics  were  as  follows: 

Date  of  birth,  August  1,  1896;  height,  146  cm. ;  range  in  body-weight  with- 
out clothing  during  experiments,  30.5  to  32.5  kilos. 

Respiration  Experiment  No.  N1. 

Date,  August  18,  1910.     Body-weight  without  clothing,  32.5  kilos. 

In  this  experiment  the  respiratory  exchange  was  determined  by  means  of 
the  respiration  apparatus,  the  subject  lying  on  a  couch.  It  is  probable  that 
he  took  food  previous  to  the  experiment.  The  experiment  beganat  8'^  12"^  a.m., 
covering  one  10-minute  period  and  ending  at  8*^  22"°  a.  m.     The  subject  was 


Table  21. —  Clinical  chart — Case  N. 


Date. 


1909. 

Aug.  27-28 

Aug.  29-30 

Aug.  30-31 

Sept.    1-2 

Sept.    2-3 

Sept.    3-4 

Sept.    7-8 

Sept.    8-9 

Sept.    9-10 

Sept.  10-11 

Sept.  12-13 

Sept.  16-17 

Sept.  22-23 

Sept.  24-25 

Sept.  26-27 

Oct.    10-11 

Oct.    17-18 

Oct.   24-25 

Oct.   31-Nov.  1. 

Nov.    9-10 

Nov.  21-22 

Nov.  23-24 

Nov.  28-29 

Dec.     1-2 

Dec.    8-9 

Dec.  12-13 

Dec.  15-16 

Dec.  19-20 

1910. 

Jan.     2-  3 

Jan.      6-7 

Jan.      9-10 

Jan.    17-18 

Feb.     3-4 

Feb.  10-11 

Mar.    4-  5 

Mar.  29-30 

Apr.   10-11 

Apr.   17-18 

May     1-2 

May  15-16 

May  23-24 

June     6-  7 

July     1-2 

July    14-15 

July   31-Aug.  1.. 

Aug.     8-9 

Aug.  23-24 

Aug.  30-31 

Sept.    2-  3 

Sept.  14-15 

Nov.  15-16 

Nov.  21-22 ^... 

Nov.  22-23 

Nov.  2.3-24 

Nov.  24-25 

Nov.  25-26 

Nov.  26-27 

Nov.  27-28 

Nov.  28-29 

Nov.  29-30 

Nov.  30-Dec.  1.. 

Dec.    U  Z 

Dec.    2-3 

Dec.    3-4 

Dec.    4-5 

Dec.    5-6 

Dec.    6-7 

Dec.    7-8 

Dec.    8-9 

Dec.    9-10 

Dec.  10-11 

Dec.  11-12 

Dec.  12-13 

Dec.  13-14 

Dec.  14-15 

Dec.  16-17 

Dec.  23-24 

Dec.  27-28 

1911. 

Jan.      6-7 

Jan.    19-20 

Feb.    5-6 

Fob.  15-16 


3  3 


c.c. 

2530 
3000 
2625 
2250 
2750 
2125 
1750 
1500 
1625 
750 
1000-1- 
2000 
2250 
1500 
1250 

i66o+ 

1250 

750 
1250+ 

750 
1500+ 
1000 
1000 
1250 

900 
1750 

1250 
1500 
750 

1666 

750 

875 
1250 
1625 
1375 
1700 
2000 
1375 
2170 
1530 
1375 
1560 
1750 
2125 
2160 
1250 
1875 
1750 

2756 
2740 
2880 
2620 
2900 
2960 
2780 
3120 
'2940 
3000 
2212 
1810 
2840 
2930 
2840 
2005 
2600 
2500 
3135 
2760 
2510 
2650 
2450 
3000 
2170 
1875 

2375 
2250 
2375 
'330 


1032 
1034 

i629 
1030 
1031 
1028 
1025 
1021 
1017 
1021 
1019 
1015 
1017 
1015 


1019 

iois 

1037 
1029 
1027 
1024 
1026 
1035 
1023 
1020 

1020 
1025 
1026 
1014 
1021 
1024 
1022 
1036 
1035 
1027 
1033 
1034 
1034 
1025 
1034 
1032 
1030 
1031 
1035 
1030 
1036 
1033 

i633 
1028 
1027 
1029 
1026 
1024 
1028 
1024 
1021 
1021 
1020 
1023 
1020 
1021 
1022 
1023 
1025 
1027 
1029 
1030 
1032 
1026 
1022 

1024 
1031 
1029 

1032 
1026 
1026 
1019 


0 
0 
0 
0 
S1.+ 
0 
0 
S1.+ 
S1.+ 
S1.+ 
S1.+ 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 

0 

S1.+ 

S1.+ 

0 

6 

+ 

S1.+ 
S1.+ 

++ 
+ 

0 

+ 

S1.+ 

++ 

++ 

+++ 

++++ 

++ 

++ 

++++ 

+++ 

++++ 

++ 

++++ 

++++ 

++++ 

++++ 

++++ 

++++ 

++++ 

+++ 

++++ 

+++ 

++++ 

+++ 

+++++ 

++ 

+++ 

++++ 

++++ 

+++ 

++ 

+ 

+++ 

+++ 

■■+++ 

++ 

++++ 

+++ 

+++ 

++++ 

0 


gms. 

n.h 


Ammonia. 


1.7 

2!6 
2!5 


2.8 
2.4 
4.2 
3  0 
2.7 
1.6 
2.3 
2.3 
2.3 
1.8 
1.6 
1.6 
2.8 
2.3 
2  4 
2.3 

212 

i!2 


I  _ 


p.  ct. 


Sugar. 


«2 


+ 

+ 
+ 

6.5 

+ 

251 

'72 

103 
84 


69 
41 
69 
58 
33 
77 
41 
61 
53 
117 
138 
180 
103 
98 
56 
70 
+ 
+ 
+ 


+ 


M 


gms. 

"6.6 

162 

156 

110 

95 

138 

85 

28 

6 

3 

0 


°  e 


4 
85 
111 
30 
95 
104 
66 
61 
89 
50 
103 
60 
119 
78 
45 
83 
46 
112 
94 
93 
92 
79 
64 
89 
67 
62 
35 
60 
49 
33 
68 
41 
51 
40 
104 
125 
163 
155 
95 
53 

'78 
78 
45 

105 
63 
62 
4 


gms. 
55=1 


80 
80 
80 
80 
15 
55 
55 
55 
15 
135 
45 
30 
35 
35 
35 
45 
45 
45 
45 


^•3 


gms. 


+  20 
+  '26 
+  '36 

+  '26 


-  15 

-  15 
10 


-  50 

-  35 

-  10 

-  15 

-  25 
+  65 

-  15 

-  10 

-  40 

-  5 

-  25 

-  10 

-  70 

-  95 
-135 


45     -120 
145     +  45 


-  10 

-  25 

-  35 

-  25 


u  « 


i>l^ 


kilos. 
29.6 
29.9 
29.9 
30.1 

36!2 

zb'.i 

30.2 
30.4 
30.4 
30.5 
31.6 
31.2 

33^4 
33.0 
32.8 
33.1 
33.0 
33.4 


33.2 

33!4 
32.1 
33.7 


33.7 


34.0 
33.3 

33^8 
33.0 
33.2 

32!? 
32.3 
32.0 


30.8 
31.3 
30.8 

3i!9 


32.3 
32.4 
32.3 
32.4 
32.7 
32.0 
31.8 

36!  i 

30.8 
31.4 
32.3 
32.1 
32.1 
32.4 
32.5 
31.8 
31.4 
31.8 
31.5 
31.4 

36!3 
30.2 


30.6 


'Percent.  'By  fermentation.  'Many  fine  and  coarse  granular  casts  in  urinary  sediment. 

*  Less  than  24  hrs.  '  Period  of  23  hrs.  45  ruin.     Vegetable  day,  including  240  c.c.  cream. 

'Period  of  24  hrs.  15  min.,  192  gms.  oatmeal,  240c. c.  cream. 
'  3  hrs.    Many  casts,  chiefly  coarse  granular,  in  urinary  sediment. 


32 


METABOLISM    IN    SEVERE    DIABETES. 


reported  as  being  restless,  opening  his  mouth  once  and  raising  his  hand  to  his 
face.  Before  coming  to  the  laboratory  the  subject  urinated  at  5  a.  m.,  and 
after  the  experiment  was  over  he  urinated  at  8*^  50™  a.  m.  The  carbon  dioxide 
eliminated  per  minute  was  181  c.c,  and  per  kilogram  per  minute  5.57  c.c.  The 
oxygen  absorbed  per  minute  was  237  c.c.  per  minute,  and  per  kilogram  per 
minute,  7.29  c.c.  The  respiratory  quotient  was  0.76.  During  the  experi- 
mental period  the  pulse-rate  averaged  73  and  the  respiration-rate,  17.  The 
urine  collected  between  5  a.  m.  and  S^  50™  a.  m.  amounted  to  145  c.c.  and  con- 
tained 0.67  gram  of  nitrogen  and  7.1  grams  of  sugar. 

Calorimeter  Experiment  No.  N2. 

Date,  December  1,  1910.     Body-weight  without  clothing,  31.2  kilos. 

For  this  experiment,  the  subject  came  to  the  laboratory  without  break- 
fast at  7'^  05™  a.  m.,  and  entered  the  bed  calorimeter  at  7'*  17™  a.  m.  The 
experiment  began  at  8^04™  a.  m.,  and  continued  for  three  45-minute  periods, 
ending  at  10^  19™  a.  m.  The  pulse  and  respiration  rates  were  obtained  by  the 
usual  methods,  but  no  records  of  the  body-temperature  were  made.  The  sub- 
ject was  very  quiet,  lying  on  his  back  and  reading  throughout  the  whole  experi- 
ment. Two  samples  of  the  alveolar  air  were  taken  both  before  and  after  the 
experiment.  Before  coming  to  the  laboratory,  the  subject  urinated  at  6''  45™ 
a.m.,  and  again  after  the  experiment  at  10''  28™  a.m.  The  records  of  the 
experiment  are  given  in  tables  22  and  25. 

Table  22. — Measurements  of  metabolism — Calorimeter  experiment  No.  N2. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 

minute. 

Total. 

Per 

minute. 

Dec.  1,  1910: 

8"   4™  a.m.  to  8"  49™  a.m 

8  49    a.m.      9    34    a.m 

9  34    a.m.     10    19    a.m 

Total  2  hrs.  15  min.^         

gms. 
12.6 
11.8 
11.0 

c.c. 
143 
1.33 
126 

gms. 
10.8 
12.8 
11.0 

c.c. 
168 
199 
171 

0.85 
.67 
.73 

76 

78 
'72 

17 
18 
19 

35.4      !        133 

34.6 

179 

1  One  record  at  10*'  03™  a.m. 

2  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.26  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  5.74  c.c. 

Calorimeter  Experiment  No.  N3. 

Date,  December  2,  1910.     Bodj^-weight  without  clothing,  30.9  kilos. 

On  the  morning  of  the  experiment  the  subject  ate  a  breakfast  consisting  of 
300  grams  of  cooked  oatmeal  and  came  to  the  laboratory  at  7^  55™  a.  m.  At 
8^  10™  a.  m.  he  entered  the  respiration  chamber  of  the  bed  calorimeter;  the 
experiment  began  at  8^  48™  a.  m.  and  continued  for  two  45-minute  periods  and 
one  53-minute  period,  ending  at  11''  11™  a.  m.  In  the  first  period  he  lay  very 
quietly  on  his  back,  reading,  but  did  not  read  in  the  second  period  and  moved 
slightly  two  or  three  times;  he  seemed  to  be  asleep  near  the  end  of  the  period. 
At  the  beginning  of  the  third  period  he  was  asleep,  but  soon  awoke  and  read  for 
a  short  time,  then  lay  quietly  without  reading.  According  to  the  observer's 
record,  the  subject  moved  considerably  more  in  this  period  than  in  the  two  pre- 
ceding, and  it  was  necessary  to  extend  the  period  8  minutes  in  order  to  obtain 
satisfactory  temperature  equilibrium  at  the  end.  Samples  of  alveolar  air  were 
taken  before  and  after  the  experiment.  The  subject  urinated  at  7  a.  m.  before 
coming  to  the  laboratory  and  again  at  11''  26™  a.  m.  after  the  experiment  was 
over.     The  records  for  the  experiment  are  given  in  tables  23  and  25. 


STATISTICS   OF   EXPERIMENTS. 


33 


Table  23. — Measurements  of  metabolism — Calorimeter  experiment  No.  N3. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 
minute. 

Total. 

Per 
minute. 

Dec.  2.  1910: 

■1 8^^  48"  a.m.  to    9^^  33""  a.m 

9    33    a.m.       10    18    a.m 

10    18    a.m.       11    11    a.m 

Total  2  hrs.  23  niin.= 

gms. 
12.4 
11.9 
14.4 

c.c. 
140 
134 
139 

gms. 
11.7 
11.4 
13.8 

c.c. 
182 
178 
182 

0.77 
.76 
.76 

79 
81 
84 

17 
14 
16 

38.7 

138 

36.9              181 

'Subject  ate  309  gms.  of  cooked  oatmeal  about  1  hr.  30  min.  before  the  experiment  began. 

"  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.47  c.c;  oxygen  absorbed  per  kilogram  per  minute,  5.8 


Calorimeter  Experiment  No.  N4. 

Date,  December  3,  1910.     Body-weight  without  clothing,  30.5  kilos. 

When  the  subject  came  to  the  laboratory  at  7''02'^  a.  m.  on  the  experi- 
mental day,  aside  from  a  small  cupful  of  black  coffee  he  had  had  no  food  since 
the  evening  meal  of  the  day  before.  After  two  samples  of  alveolar  air  had  been 
taken,  he  entered  the  bed  calorimeter  at  1^  23"  a.  m.  The  experiment  began 
at  8"^  08™  a.  m.,  continued  for  three  45-minute  periods,  and  ended  at  10^  23"* 
a.  m.  The  subject  was  very  quiet  throughout  the  experiment,  reading  most 
of  the  time  except  near  the  end  of  each  period;  he  did  not  sleep  at  all.  After 
the  experiment  was  over,  he  urinated  at  10''  35™  a.  m. ;  two  additional  samples 

Table  24. — Measurement  of  metabolism — Calorimeter  experiment  No.  N4- 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxj-gen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 

minute. 

Total. 

Per 

minute. 

Dec.  3,  1910: 

1 8^  08™  a.m.  to    8*'  53"'  am 

8  53    a.m.        9    38    a.m 

9  38    a.m.       10    23    a.m 

ams. 
11.0 
10.2 
11.0 

c.c. 
124 
116 
124 

gms. 
10.8 
9.8 
10.3 

c.c. 
168 
152 
161 

0.74 
.76 

.77 

56 

58 
58 

14 

14 
13 

32.2 

121 

30.9 

160 

>  Subject  drank  a  small  cup  of  black  cofifee  about  1  hr.  15  mins.  before  the  experiment  began. 

2  Carbon  dio.xide  eliminated  per  kilogram  per  minute,  3.97  c.c;  oxygen  absorbed  per  kilogram  per  minute,  5.25  c.c. 

of  alveolar  air  were  also  taken.  The  subject  said  that  he  did  not  feel  quite  so 
tired  and  hungry  as  he  had  at  the  close  of  preceding  experiments.  On  the 
morning  of  December  5  his  mother  said  that  during  the  afternoon  of  the  exper- 
imental day  and  all  the  next  day  the  subject  was  much  brighter  and  better 
than  he  had  been  for  some  time.     He  was  quite  lively  and  in  good  spirits, 

Table  2o.— Statistics  of  urine — Calorimeter  experiments  Nos.  N2-N4- 


Date  and  period. 


Volume. 


Dec.  1,  1910:  6''4.5'"  a.m.  to  lO**  38™  a.m. 
Dec.  1-2,  1910:  lO*"  38"^  a.m.  to  7°  a.m.. . 

Dec.  2,  1910:  7  a.m. i  to  U'^  26™  a.m 

Dec.  2-3,  1910:  U'^  26'"  a.m.  to  7  a.m. . . 

Dec.  3, 1910:  7  a.m.2  to  lOl^  35"  a.m 

Dec.  3-4,  1910:  10°  35"  a.m.  to  7  a.m. . . . 


c.c. 

473 
2520 

512 
1700 

250 
1560 


Specific 
gravity. 


1.019 
1.020 
1.022 


Total 
nitrogen. 


gms. 
1.26 
4.86 
.98 
5.09 
95 
4.11 


Sugar. 


gms. 

5.7 
64.8 
17.9 
4n.6 

8.1 
29.4 


'  Subject  ate  300  gms.  of  cooked  oatmeal  just  before  coming  to  the  laboratory  at  7''  55 
'Subject  drank  a  small  cup  of  black  coffee  just  before  coming  to  the  laboratory  at  7° 


02""  a.m. 


34 


METABOLISM   IN   SEVERE   DIABETES. 


although  previously  he  had  been  very  melancholy  and  his  physical  condition 
had  preyed  upon  his  mind  so  that  he  had  not  been  at  all  happy.  The  meas- 
urements of  metabolism  and  the  average  pulse  and  respiration  rates  are  given 
in  table  24,  and  the  statistics  of  urine  in  table  25. 

Calorimeter  Experiment  No.  N5. 

Date,  December  5,  1910.     Body-weight  without  clothing,  31.7  kilos. 

For  this  experiment  the  subject  came  to  the  laboratory  at  7^  05™  a.  m., 
without  breakfast,  and  entered  the  bed  calorimeter  at  7''  29"^  a.  m. ;  the  experi- 
ment began  at  8^  22'"  a.  m.,  ending  at  10'^  38°^  a.  m.,  after  three  45-minute 
periods.  Throughout  the  whole  period  the  subject  was  quiet,  reading  much 
of  the  time.  Samples  of  the  alveolar  air  were  taken  both  before  and  after  the 
experiment.  The  subject  urinated  at  7  a. m., before  coming  to  the  laboratory, 
and  at  lO*"  56°"  a.  m.  after  the  experiment  was  over.  He  said  at  the  conclusion 
of  the  experiment  that,  while  he  was  tired  and  sleepy  and  somewhat  hungry,  he 
felt  quite  well.     The  records  of  the  experiment  are  given  in  table  26. 

Table  26. — Measurements  of  metabolism — Calorimeter  experiment  No.  N5. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Ox>'gen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 

minute. 

Total. 

Per 

minute. 

Dec .  .5.  1910- 

8^  22™  a.m.  to  9'^  07™  a.m 

9    07    a.ra.        9    52     a.m 

9    52     a.m.       10    38    a.m 

Total  2  hrs.  16  min.' 

gms. 
11.2 
10.5 
11.9 

c.c. 
127 
119 
132 

gms. 
11.1 
11.1 
11.1 

c.c. 
172 
172 
168 

0.74 
.60 

.78 

54 
55 
58 

16 
16 
16 

33.6 

126 

33.3 

171 

1  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.97  c.c;  oxygen  absorbed  per  kilogram  per  minute,  5.39 
c.c.  The  urine  collected  between  7  a.m.  and  10^  56™  a.m.  amounted  to  590  c.c.  and  contained  1.96  gms.  of  nitrogen 
and  8.8  gms.  of  sugar. 

Calorimeter  Experiment  No.  N6. 

Date,  December  7,  1910.     Bodj^-weight  without  clothing,  32  kilos. 

The  subject  arrived  at  the  laboratory  without  breakfast  at  7'' 05°"  a.m. 
The  experiment  began  at  8''  20°^  a.  m.  and  continued  for  three  45-minute 
periods,  ending  at  10'' 35"  a.  m.  Throughout  the  experiment  the  subject  lay 
on  his  back,  quietly  reading.  He  did  not  sleep  at  all.  As  usual  samples  of 
alveolar  air  were  taken  before  and  after  the  experiment.  Before  coming  to  the 
laboratory  the  subject  urinated  at  Q^  30™  a.  m.  and  at  lO''  50"'  a.  m.,  after  the 
experiment  was  over.  On  coming  out  of  the  bed  calorimeter  the  subject  com- 
plained of  no  discomfort,  saying  only  that  he  was  quite  hungry.  The  records 
of  the  experiment  are  given  in  table  27. 

Table  27. — Measurements  of  metabolism — Calorimeter  experiment  No.  N  6. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total.          y^\ 
minute. 

Total. 

Per 
minute. 

Dec.  7,  1910: 

8**  20™  a.m.  to    9'^  05™  a.m 

9    05    a.m.        9    50     a.m 

9    50    a.m.       10    35     a.m 

gms.            c.c. 
11.4              129 
12.2              139 
10.9              122 

gms.             c.c. 
11.2              174 
11.7              181 
11.1       1        172 

0.74 
.77 
.71 

56 
57 
57 

17 
17 
16 

Total  2  hrs.  15  min.i 

34.5 

130 

34.0               176 

1  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.06  c.c.;  oxygen  absorbed  per  kilogram  per  minute,  5.50 
c.c.  The  urine  collected  betweon  6°  30™  a.m.  and  lO''  50™  a.m.  amounted  to  545  c.c,  specific  gravity  1.019,  and 
contained  1.90  gms.  of  nitrogen  and  7.9  gms.  of  sugar. 


STATISTICS    OF   EXPERIMENTS. 


35 


Calorimeter  Experiment  No.  N7. 

Date,  December  10,  1910.     Body-weight  without  clothing,  31.8  kilos. 

The  subject  arrived  at  the  laboratory  at  7^  10™  a.  m.,  without  breakfast. 
Before  he  entered  the  bed  calorimeter  at  7^33"  a.  m.,  samples  of  alveolar  air 
were  taken  and  a  record  made  of  the  ventilation  of  the  lungs.  The  experiment 
began  at  8'^  22™  a.  m.,  ending  at  10"^  40™  a.  m.,  after  three  45-minute  periods. 
At  9'"  56™  a.  m.  the  subject  drank  76  c.c.  of  water.     During  the  first  period  he 

Table  28. — Measurements  of  metabolism — Calorimeter  experiment  No.  N  7. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Averase 
respira- 
tion rate. 

Total. 

Per 
minute. 

Total. 

Per 
minute. 

Dec.  10,  1910: 

S*"  22™  a.m.  to    9^^  07™  a.m 

9    07    a.rn.        9    54    a.m 

9    54    a.rn.       10    40    a.m 

Total  2  hrs.  18  min.i 

gms. 
12.9 
12.6 
13.0 

c.c. 
146 
137 
143 

gtns. 
11.9 
12.4 
12.6 

c.c. 
184 
184 
192 

0.79 
.75 
.75 

75 
77 
81 

19 
18 
18 

38.5 

142 

36.9 

187 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.47  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  5.88  c.c 

was  very  quiet,  reading.  He  did  not  read  during  the  second  period,  but  lay 
very  quietly,  and  slept  about  20  minutes.  In  the  third  period,  however,  he 
moved  considerably  and  gave  evidence  of  being  very  restless.  Samples  of  the 
alveolar  air  were  also  taken  after  the  experiment.  The  subject  urinated  before 
the  experiment  at  Q^  45™  a.  m.  and  after  the  experiment  at  ll*"  05™  a.  m.  The 
data  regarding  the  metabolism  measurements  and  the  average  pulse  and  respi- 
ation  rates  are  given  in  table  28  and  the  statistics  of  urine  in  table  29. 

Table  29. — Statistics  of  urine^Calorimeter  experiment  No.  N7. 


Date  and  period.                                      Volume. 

Specific 
gravity. 

niTroSn.          «--• 

Dec.  10,  1910:  e*"  45™  a.m.  to  11^05™  a.m 

c.c. 
475 
2660 

1.027 
1.031 

gms. 
1.47 
6.66 

gms. 
15.2 
164.0 

Dec.  10-11,  1910:  ll'»OJ™a.m.  to  e*"  45™  a.m 

Calorimeter  Experiment  No.  N8. 

Date,  December  12,  1910.     Body-weight  without  clothing,  31.7  kilos. 

The  subject  reached  the  laboratory  at  7  a.  m.,  without  breakfast,  and 
entered  the  bed  calorimeter  at  7''  38™  a.  m.,  after  two  samples  of  the  alveolar  air 
had  been  taken  and  records  made  of  the  ventilation  of  the  lungs.  A  blood- 
pressure  of  90  mm.  was  also  recorded  at  7*^  30™  a.  m.  The  experiment  began  at 
9  a.  m.,  continuing  for  two  30-minute  and  one  40-minute  periods,  ending  at 
10^  40™  a.  m.  The  pulse  and  respiration  rates  were  obtained  as  usual  by  the 
stethoscope  and  pneumograph.  The  telephone  was  used  once  during  the 
experiment,  at  the  beginning  of  the  first  period,  but  otherwise  the  subject  was 
very  quiet,  reading  nearly  all  of  the  time  except  near  the  end  of  each  period. 
Samples  of  the  alveolar  air  were  taken  at  the  end  of  the  experiment,  as  usual. 
Before  coming  to  the  laboratory,  the  subject  urinated  at  6'^  45™  a.  m.,  and  again 
at  11*^  08™  a.  m.,  after  the  experiment  was  over.  No  water  was  taken  during 
the  experiment.  The  data  regarding  the  metabolism  measurements  and  the 
average  pulse  and  respiration  rates  are  given  in  table  30  and  the  statistics  of 
urine  in  table  31. 


36 


METABOLISM    IN    SEVERE   DIABETES. 


Calorimeter  Experiment  No.  N9. 

Date,  December  14,  1910.     Body-weight  without  clothing,  31.4  kilos. 

The  subject  arrived  at  the  laboratory  without  breakfast  at  7^  10""  a.  m., 
and  entered  the  bed  calorimeter  at  7^  32"^  a.  m.  The  experiment  began  at 
8^  21""  a.  m.,  continuing  for  two  45-minute  periods  and  one  40-minute  period, 

Table  30. — Measurements  of  metabolism — Calorimeter  experiment  No.  NS. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed.       Respi- 

Average 
pulse - 
rate. 

Average 
respira- 
tion rate. 

T^toi      1      Per 
T°tal-       minute. 

Totfll            P®""      !  quotient. 
^°'^^'-       minute.   | 

Dec.  12,  1910: 

9^  00™  a.m.  to   9*^  30™  a.m 

9    30    a.m.       10    00    a.m 

10    00    a.m.       10    40    a.m 

Total  1  hr.  40  min.' 

gms.            c.c. 
8.0              135 
7.5              127 

10.0              128 

gms. 
8.2 
7.5 

10.1 

192      1      0.70 
173      1         .73 

176      1         .72 

59 
61 
61 

15 
15 
15 

25.5      j        130 

25.8             181      !      ....       1        ..        !        ..        1 

1 

1  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4. 10  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  5.71  c.c. 

ending  at  lO*'  31""  a.  m.  As  usual  with  this  subject,  he  lay  quietly  reading  dur- 
ing practically  the  whole  experiment,  save  at  the  beginning  of  the  third  period, 
when  he  moved  quite  a  little.  Samples  of  alveolar  air  were  taken  and  records 
made  of  the  ventilation  of  the  lungs  both  before  and  after  the  experiment;  a 

Table  31. — Statistics  of  urine — Calorimeter  experiment  No.  N  8. 


Date  and  period. 

Volume. 

Specific 
gravity. 

Total 
nitrogen. 

Sugar. 

Dec.  12,  1910: 

e*- 45"  a.m.  to  lib  08«>  a.m 

Dec.  12-13,  1910: 

ir  08™  a.m.  to  e""  45™  a.m 

c.c. 
350 

2160 

1.032 
1.026 

gms. 

1.84 

5.99 

gms. 
16.7 

80.0 

record  of  90  mm.  for  the  blood-pressure  was  obtained  at  7''  10™  a.  m.  The  sub- 
ject urinated  at  7  a.  m.,  before  coming  to  the  laboratory,  and  at  10''  55""  a.m., 
after  the  experiment  was  over.  No  water  was  taken.  The  results  of  the 
experiment  are  given  in  table  32. 

Table  32. — Measurements  of  metabolism — Calorimeter  experiment  No.  N9. 


Date  and  period. 

Carbon  dioxide      \   ^              u      u  a 
eliminated.             Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

14 
15 
14 

Total. 

Per 
minute. 

Total. 

Per 

minute. 

Dec.  14,  1910: 

8'' 21™  a.m.  to   g'' 06™  a.m 

9    06    a.m.        9    51    a.m 

9    51    a.m.      10    31    a.m 

Total2hrs.  10  min.'... 

gms. 
11.0 
10.8 
9.6 

c.c. 
126 
121 
121 

gms. 
10.9 
12.0 
9.4 

169           0.74 
187              .65 
164               .74 

61 

58 
58 

31.4 

123 

32.3 

174 

Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.92  c.c:  oxygen  absorbed  per  kilogram  per  minute,  5.54 
c.c.  The  urine  collected  between  7  a.m.  and  10^  55™  a.m.  amounted  to  390  c.c,  specific  gravity  1.025,  and  contained 
1.49  gms.  of  nitrogen  and  10.6  gms.  of  sugar. 

CASE  0. 
DESCRIPTION   OF   THE    CASE. 

Female;  born  August  16,  1894;  single;  no  occupation;  onset  of  diabetes  at 
age  of  13,  February  1908;  sugar  in  urine,  March  1908;  came  under  our  obser- 
vation April  18,  1908;  died  in  coma  December  10,  1910. 


STATISTICS    OF   EXPERIMENTS. 


37 


Family  history. — No  history  of  diabetes  in  the  family.  Father  died  of 
pneumonia;  mother  and  brother  well. 

Past  history. — Scarlet  fever,  dysentery  at  3  years  of  age,  measles,  mumps, 
whooping-cough,  chicken-pox,  enuresis  nocturna  which  ceased  at  the  age  of  4. 
Had  always  a  voracious  appetite,  sometimes  eating  six  potatoes  at  a  meal;  ate 
much  candy. 

General  history  of  the  case. — During  the  yearpreceding  the  onset  of  the  dis- 
ease the  patient  developed  rapidly  both  in  height  and  weight.  In  February 
1908,  she  showed  weariness.  Early  in  March,  polydipsia,  polyuria,  and  poly- 
phagia were  present,  and  sugar  was  demonstrated  in  the  urine.  One  year  pre- 
vious the  urine  had  been  examined  and  was  said  to  l^e  normal. 

During  the  whole  period  of  illness  the  patient  remained  in  good  condition 
and  attended  school  with  comfort.  The  diet  was  rigidly  adhered  to  and  not 
relaxed  except  when  the  diagnosis  was  at  one  time  doubted  by  the  local  physi- 
cian. Catamenia  was  established  for  the  first  time  in  March  1909.  No 
essential  change  in  the  physical  examination  took  place.  The  patient  died  in 
coma  on  December  10,  1910. 

Table  33. — Comparison  of  metabolism  experiments  in  bed  calorimeter  with  Case  N. 
EXPERIMENTS  WITHOUT  FOOD. 


Experi- 
ment 
No. 

Date. 

Weight  of 
subject. 

Length 
of  experi- 
ment. 

Per  minute. 

Respi- 
ratory- 
quotient. 

Average 
pulse  per 
minute. 

Average 
respira- 
tion per 
minute. 

Carbon 

dioxide 

eliminated. 

Oxygen 
absorbed. 

N2 
N4 
N5 
N6 
N  7 
N8 
N9 

1910. 
Dec.    1 
Dec.    31 
Dec.    5 
Dec.    7 
Dec.  10 
Dec.  12 
Dec.  14 

kilos. 
31.2 
30.5 
31.7 
32.0 
31.8 
31.7 
31.4 

hr.  jtiin. 
2      15 
2      15 
2      16 
2      15 
2      18 

1  40 

2  10 

c.c. 
133 
121 
126 
130 
142 
130 
123 

c.c. 
179 
160 
171 
176 
187 
181 
174 

0.74 
.76 
.73 
.74 
.76 
.72 
.71 

75 
57 
56 
57 
78 
60 
59 

18.0 
13.5 
16.0 
16.5 
18.5 
15.0 
14.5 

EXPERIMENT  WITH  FOOD. 

N3 

1910.           kilos.        hr.  min. 
Dec.    2  2        30.9          2      23 

c.c.                 c.c. 

138                  181              0.76 

81 

15.5 

'About  1  hr.  15  min.  before  experiment  began,  subject  drank  a  small  cup  of  black  coffee. 
-About  1  hr.  30  min.  before  the  experiment  began,  subject  ate  300  gms.  of  cooked  oatmeal. 

Physical  examination.- — A  healthy  appearing  girl.  Greatest  weight,  Janu- 
ary 1908,  60.8  kilos,  without  clothing;  weight,  April  20, 1908,49.2  kilos,  without 
clothing.  Height,  173  cm.  No  acetone  odor.  Pupils  equal  and  reacted  to 
light;  tongue  and  teeth  normal.  Few  cervical  and  axillary  glands.  Apex  of 
heart  within  nipple  line;  no  murmurs.  Nothing  abnormal  felt  in  abdomen. 
Knee-jerks  normal.  The  greatest  quantity  of  urine  was  approximately  5,000 
c.c,  just  previous  to  April  18,  1908. 

Urine  data. — The  course  of  the  disease  is  given  in  table  34.  Although  the 
urine  showed  4.8  per  cent  of  sugar  on  April  18,  1908,  it  will  be  seen  that  under 
the  restriction  of  the  carbohydrates  to  approximately  10  grams  the  urine 
became  sugar-free.  The  tolerance  for  carbohydrates  gradually  increased,  and 
reached  approximately  90  grams  of  carbohydrates  in  February  1909,  where  it 
remained  until  after  October  28,  1909.  The  weight  rose  from  49.2  kilos.,  April 
20,  1908,  to  55.8  kilos.,  July  28,  1909.  The  health  was  so  good  that  the  local 
physician  would  not  believe  that  the  patient  had  diabetes,  and  allowed  a  free 
diet  on  Thanksgiving  Day,  1909.  Sugar  returned  early  in  December  1909,  but 
disappeared  at  once  when  the  diet  was  again  restricted.     A  tolerance  of  55 


2091 8 J 


38 


METABOLISM   IN    SEVERE   DIABETES. 


grams  of  carbohydrate  was  reached  February  18,  1910,  but  after  April  21  of 
that  year  sugar  was  seldom  absent  until  the  patient's  death. 

The  reaction  of  the  urine  was  acid  throughout,  except  upon  April  30, 1908. 
Diacetic  acid  was  present  when  the  patient  was  first  seen,  but  disappeared 
when  the  urine  became  sugar-free,  not  returning  until  September  1910.  The 
/3-oxybutyric  acid  reached  14.3  grams  upon  September  23-24,  1910,  but  the 
ammonia  was  low,  which  was  due  in  part  to  the  sodium  bicarbonate  admin- 
istered. 

Table  34. — Clinical  chart — Case  0. 


Date. 


Sugar. 


S3 

73  O 


1908. 
Apr.  lS-19. 
Apr.  19-20. 
Apr.  20-21. 
Apr.  21-22. 
Apr.  22-23. 
Apr.  23-24. 
Apr.  24-25. 
Apr.  25-26. 
Apr.  26-27. 
Apr.  27-28. 
May     1-  2. 

1910. 
Sept.  8-9. 
Sept.  9-10. 
Sept.  10-11. 
Sept.  11-122 
Sept.  12-13. 
Sept.  13-14. 
Sept.  14-15. 
Sept.  15-16  , 
Sept.  16-17., 
Sept.  17-183 
Sept.  18-19  < 
Sept.  19-20  * 
Sept.  20-21.. 
Sept.  21-22.. 
Sept.  22-235 
Sept.  23-24  6 
Sept.  24-255. 
Sept.  25-26.. 
Sept.  26-27.. 
Oct.  3-4.. 
Oct.  13-14.. 
Oct.  25-26.. 
Nov.  16-17.. 
Nov.  29-30.. 


c.c. 

1800 

2610 

1710 

1890 

1600=1 

1650 

1650 

1590 

2970 

1650 

1830 

U140 
1830 
2200 
2640 
2340 
1470 
2760 
2760 
2940 
1440 
2820 
3420 
3420 
2880 
3280 
2577 
2410 
3270 
2460 
1860 
2210 
2300 
1750 
2000 


1017 
1030 

1627 
1025 
1025 
1019 
1024 
1015 
1028 
1023 
1026 
1022 
1025 

1021  I 

1023  I 
1025 

1022  ' 

1024  ! 
1029 
1028 
1029 
1034 
1031 


++ 
++ 

+ 


+ 
0 
0 

0 

+ 

++ 

+ 

+ 

+ 

+-H 

+++ 
+++ 

+++ 

0 

+++ 

-l-h+ 
+++ 
++ 
++ 
+++ 
+++ 

++-H 

++++ 

+++ 


13.0 
14.3 
14.1 


20.1 


13.0 


20.7 
20.1 

\Y.2 
15.6 
18.3 

8.7 
13.6 
12.9 
15.2 
14.1 
11.2 

8.0 
10.0 
11.1 
12.6 

ii.'g 

15.9 


p.  ct. 


7.8 


5.7 


3.6 
3.8 
3.0 


4.4 
5.1 


6.7 
6.5 


11.0 
12.4 


gms. 
50 
78 
44 
60 
42 
20 
17 
16 
12 


gms. 
90 
90 
64 
60 
60 
40 
20 
15 
10 
12 
16 


10 
10 
10 
10 
10 
10 
10 
10 

145 
15 
15 
15 
15 
15 

165 
15 
15 
15 
20 


gms. 
+  40 
-I-  10 
+  20 

-f-'26 
+  20 

8  1+    5 


+  10 
+  15 


-  35 

-  35 

-  45 

-  25 


-  20 

-  35 

+120 

-'36 

-  25 

-  40 

-  25 
+115 

-  5 

-  40 
40 

-  40 


kilos. 

49  .'2 
49.2 
49.2 
49.4 
49.5 
49.6 
50.2 
.50.4 
50.0 
50.2 

50.9 
50.9 
51.4 
51.3 
52.2 
52.3 
52.4 
52.4 
51.6 
52.0 
53.0 
52.3 
52.7 
52.8 
52.9 
52.3 
52.6 
52.3 

52^5 
54.2 
53.6 

5216 


>  12  hour.s.  2  Vegetable  day.  ^  Oatmeal  day  with  120  c.c.  cream  and  215  gms.  butter. 

'Vegetable  day,  with  240  c.c.  cream.  'Vegetable  day,  240  c.c.  cream,  4  eggs. 

6  Oatmeal  day,  240  gms.  oatmeal,  240  gms.  butter,  120  c.c.  cream. 


EXPERIMENTS   WITH    CASE    O. 

Four  respiration  experiments  were  carried  out  with  this  subject,  of  vary- 
ing character.     The  vital  statistics  are  as  follows: 

Date  of  birth,  August  16,  1894;  height,  173  cm.;  range  in  body-weight 
without  clothing  during  experiments,  52.3  to  52.8  kilos. 

Respiration  Experiment  No.  01. 

Date,  September  22,  1910.     Body-weight  without  clothing,  52.8  kilos. 

On  the  day  of  the  experiment  the  subject  reached  the  laboratory,  fasting, 
at  8*"  05°^  a.m.,  and  lay  down  on  the  couch  immediately  after  the  pneumograph 
had  been  adjusted.  The  stethoscope  was  not  used  in  this  experiment,  the  pulse- 


STATISTICS   OF   EXPERIMENTS. 


39 


rate  being  counted  at  the  wrist.  The  experiment  began  at  8^  23""  a.  m.,  con- 
tinuing for  three  periods  of  11  to  13  minutes,  with  intermissions  of  10  to  17 
minutes,  ending  at  9''26"'  a.  m.  The  subject  remained  quiet  throughout  all 
three  periods,  except  for  raising  her  hand  to  her  head  once  in  the  first  period. 
The  surgeon's  plaster  was  not  used  to  close  the  mouth,  nor  did  it  appear  to  be 
necessary.  The  subject  urinated  at  7  a.  m.,  and  again  after  the  experiment  at 
9^  30™  a.  m.     The  results  are  given  in  tables  35  and  39. 

Table  35. — Results  of  respiration  experiment  No.  01. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 

per 
minute. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 

respira- 

rate. 

Sept.  22,  1910: 

8'»23'»a.m 

8  53    a.m 

9  15    a.m 

tnin.  sec. 
12    51 
12    29 
10    36 

c.c. 
167 
165 
167 

c.c. 
231 
219 
228 

0.73 
.75 
.73 

62 
63 
68 

17 
18 
IS 

J 166 

1226 

0.74 

64 

18 

per  kilogram  per  minute,  4.28  c.c. 

Respiration  Experiment  No.  02. 

Date,  September  22,  1910.     Body-weight  without  clothing,  52.8  kilos. 

This  experiment  was  carried  out  in  the  afternoon  of  the  clay  on  which 
experiment  No.  01  was  made,  after  food  had  been  taken.  The  diet  for  this  day 
was  that  of  a  regular  vegetable  day,  with  the  addition  of  4  eggs  and  one-half 
pint  of  cream.  The  subject  arrived  at  the  laboratory  at  about  3  p.  m.,  and 
immediately  lay  down  upon  the  couch.  The  experiment  began  at  3*'  12™  p.m., 
continued  for  three  periods  11  to  12  minutes  in  length,  with  the  usual  inter- 
missions, and  ended  at  4^  16™  p.  m.  During  the  second  period,  some  difficulty 
was  experienced  in  obtaining  a  record  of  the  pulse-rate.  The  subject  was 
extremely  quiet  throughout  the  whole  experiment.  The  records  are  given  in 
tables  36  and  39. 

Table  36. — Results  of  respiration  experiment  No.  02. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Sept.  22,  1910: 

i3l>12"p.m.... 

3  39    p.m 

4  06    p.m.... 

min.  sec. 
12      2 
12      3 
10      5 

c.c. 
208 
213 
197 

c.c. 
284 
299 
267 

0.73 
.71 
.74 

64 
2  72 
69 

21 
17 
19 

3  206 

3  283 

0.73 

19 

'The  subject  had  probably  taken  food  before  thi.s  experiment.  2 One  record  at  3"  47"  p.m. 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.90  c.c;  oxygen  absorbed  per  kilogram  per  minute,  5.36  c.c. 

Respiration  Experiment  No.  03. 

Date,  September  23,  1910.     Body-weight  without  clothing,  52.3  kilos. 

The  experiment  was  made  on  an  oatmeal  day,  the  first  being  a  fasting 
period,  and  the  second  period  following  an  oatmeal  breakfast.  The  subject 
then  returned  to  the  hospital,  but  after  a  dinner  containing  oatmeal,  came 
back  to  the  laboratory  and  two  additional  periods  followed.  The  experiment 
was  concluded  by  two  periods  after  the  subject  had  been  again  to  the  hospital 
and  eaten  a  lunch  containing  oatmeal. 

In  the  morning  she  reached  the  laboratory  at  7''  55"  a.  m.,  without  break- 
fast, and  lay  on  the  couch  about  10  minutes  before  the  experiment  began  at 


40 


METABOLISM   IN    SEVERE    DIABETES. 


8^  15'"  a.  m.  There  was  but  one  15-minute  period  at  this  time,  the  subject 
lying  very  quietly  throughout. 

Immediately  after  the  fasting  period  was  over,  she  was  given  oatmeal, 
which  was  eaten  between  8''  45"'  a.  m.  and  8*^  53'"  a.  m.  She  again  lay  down 
upon  the  couch  at  9'^  46'"  a.  m.;  the  next  period  began  at  10^  01"^  a.  m.,  con- 
tinuing for  15  minutes.     The  subject  was  very  quiet  throughout  the  period. 

At  2  p.  m.  the  subject  returned  from  the  hospital,  and  immediately  on  her 
arrival  at  the  laboratory  Isiy  down  upon  the  couch.  The  measurements  were 
begun  at  2^  15""  p.  m.,  continuing  for  two  periods,  10  and  12  minutes  long, 
respectively,  with  an  intermission  of  15  minutes.  No  blanket  was  used  to 
cover  the  subject,  as  she  seemed  comfortable  without  it. 

For  the  later  periods,  the  subject  came  to  the  laboratory  at  5''  30""  p.  m., 
and  the  measurements  began  at  5''  38"'  p.  m.,  continuing  for  two  periods  of  12 
and  13  minutes  each,  with  an  intermission  of  10  minutes.  As  in  the  previous 
periods,  the  subject  lay  very  quietly. 

The  results  of  the  measurements  are  given  in  tables  37  and  39. 


Table  37 

— Results  of  respiration  experiment  No.  OS. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 

Respi- 

Average 

Average 

Date  and  time. 

Duration. 

absorbed 

ratory 

pulse- 

respira- 

per minute. 

quotient. 

rate. 

tion  rate. 

Sept.  23,  1910: 

min.  sec. 

c.c. 

c.c. 

Without  food— 

8h  15™a.m 

14    45 

U65 

1232 

0.71 

60 

18 

After  oatmeal — - 

10l>01™a.m.... 

15      1 

175 

235 

.74 

66 

18 

2    15    p.m.... 

11     55 

175 

257 

.68 

64 

17 

2    42    p.m 

10      9 

180 

254 

.71 

68 

17 

5    38    p.m 

12      9 

183 

262 

.70 

72 

16 

6    00    p.m.... 

12    45 

194 

276 

.70 

70 

16 

3181 

3  257 

.71 

68 

17 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  without  food,  3.15  c.c;  oxygen  absorbed  per  kilogram 

per  minute,  without  food,  4. 44  c.c. 
-Subject  ate  oatmeal  between  8°  45""  a.m.  and  8    53"^  a.m.  and  throughout  the  day.     (See  notes.) 
'Carbon  dioxide  eliminated  per  kilogram  per  minute,  with  food,  3.46  c.c;  oxygen  absorbed  per  kilogram 

per  minute,  with  food,  4.91  c.c. 

Respiration  Experiment  No.  04. 

Date,  September  24,  1910.     Body-weight  without  clothing,  52.6  kilos. 

The  subject  arrived  at  the  laboratory,  without  breakfast,  at  8''  03"*  a.  m., 
and  immediately  lay  down  upon  the  couch.  The  experiment  began  at  8^  17"" 
a.  m.,  continuing  for  two  periods  of  12  and  13  minutes,  with  an  intermission  of 
13  minutes.  In  both  periods  she  was  very  quiet,  only  one  slight  movement  of 
the  hands  in  the  second  period  being  noted.  As  the  subject  seemed  tired  at  the 
end  of  the  second  period,  the  experiment  was  discontinued.  The  results  are 
given  in  tables  38  and  39. 

Table  38. — Results  of  respiration  experiment  No.  04- 


Date  and  time. 


•  dioxide     i     O^^'Sen     '     Respi-    |  Average  |  Average 

Duration.  eiirnin„i-g(]     absorbed        ratory         pulse-        respira- 

''  Der  minute     ^^  minute.  '  quotient,  i      rate.       tion  rate. 


Sept. ,24,  1910:  viin.  sec.  \  c.c. 

8''17™a.m 12      6    |  155 

8    42    a.m I     12    42  149 


213 

209 


0.73 
.71 


>211 


59 


'Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.89  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.01  c 


STATISTICS    OF    EXPERIMENTS. 


41 


Table  39. — Sialistics  of  urine — Respiration  experiments  Nos.  Ol-O. 


Date  and  period. 

Volume. 

Specific 
gravity. 

Total 
nitrogen. 

Sugar. 

Sept.  22,  1910: 

y'' 00™  a.m.  to    9'^30"'a.m 

ex. 
520 

1.010 

gms. 
0.91 

gms. 
4  2 

9    30    a.m.       10    00    a.m 

165 

1.024 

,62 

2.5 

10    00    a.m.       12    noon 

600 

1.019 

1.64 

7  8 

12    00    noon         3    00    p.m.' 

240 

1.025 

.74 

4.1 

3    00    p.m.         6    00    p.m 

300 

1.029 

1.33 

3,4 

6    00    p.m.         8    1.5    p.m 

315 

1.029 

1.27 

3,4 

8    15    p.m.       11    45    p.m 

390 

1.031 

1.87 

5  7 

Sept.  22-23.  1910: 

11*^  45™  p.m.  to    7^  00™  a.m 

7.50 

1.024 

3.00 

11  0 

Sept.  23,  1910: 

71^00™  a.m.  to    9'' 10™  a.m.=  .. . . 

432 

1.016 

1.08 

5.9 

9    10    a.m.       11    30    a.m 

480 

1.022 

1,39 

9.3 

11    30    a.m.         4    00    p.m 

420 

1.018 

1.21 

6.3 

4    00    p.m.         7    15    p.m 

330 

1.027 

1.04 

6.4 

7    15    p.m.         9    20    p.m 

285 

1,026 

.79 

5,6 

Sept.  23-24. 1910: 

9''  20™  p.m.  to    2''  15™  a.m 

420 

1.034 

1.49 

8,3 

Sept.  24,  1910: 

2*1  15™  a.m.  to    7'^  00™  a.m 

210 

1.0.35 

1,05 

4,1 

7    00    a.m.  to    7    00    p.m 

1250 

1.025 

5,08 

5,9 

Sept.  24-25,  1910: 

7^' 00™  p.m.  to    7'' 00™  a.m 

1162 

1.023 

4.89 

313,1 

1  Food  was  probably  eaten  at  about  noon. 

2  Oatmeal  wa.s  eaten  between  81"  45™  a.m.  and  &>  53" 
'Sugar  by  fermentation. 

CASE  P. 


a.m.  and  throughout  the  day. 


DESCRIPTION    OF   THE    CASE. 


Male;  born  May  10,  1894;  single;  no  occupation;  lost  strength  in  Decem- 
ber 1910;  came  under  our  observation  September  1911;  diagnosis  of  diabetes, 
which  was  confirmed  by  his  physician,  in  January  1911 ;  died  in  coma  November 
5,  1911. 

Family  history. — Father  and  one  sister  well;  mother  in  poor  health;  one 
sister  died  at  2  months,  cause  unknown.     No  history  of  diabetes  in  the  family. 

Past  /iisior?/.— Measles.  Always  good  health.  As  the  family  moved  fre- 
quently from  place  to  place  he  was  much  retarded  in  his  studies  at  school ;  this 
caused  him  much  anxiety,  and  he  consequently  worked  very  hard. 

General  history  oj  the  case. — In  December  1910,  at  the  age  of  17,  his  health 
failed,  and  the  disease  was  diagnosed  as  diabetes  in  January  1911.  He  suffered 
from  numerous  furuncles  which  did  not  yield  to  local  treatment,  or  treatment 
with  vaccines.  Worn  out  by  these,  the  patient  gradually  failed,  and  suc- 
cumbed to  coma  on  November  5,  1911. 

Physical  examination. — Greatest  weight,  49.9  kilos.;  usual  weight,  48.6 
kilos.;  January  1911,  45.8  kilos.;  September  16,  1911,  42.1  kilos.;  all  weights 
without  clothing.  Height,  173  cm.  Acetone  odor  to  breath.  Examination 
negative  except  for  numerous  furuncles,  especially  about  the  neck. 

Urine  data. — The  quantity  of  urine  in  January  1911  was  approximatelj^ 
5,000  c.c.  The  sugar  disappeared  after  treatment  for  a  month,  but  then  per- 
manently returned.  The  reaction  of  the  urine  was  acid  throughout  the  period 
of  observation.  The  ammonia  amounted  to  3.3  grains  shortly  after  the  patient 
came  under  observation  in  September  1911,  rising  to  6.5  grams  October  14-15. 
The  acidosis  was  so  considerable  that  no  great  restriction  of  diet  was  attempted. 
The  albumen  never  exceeded  a  very  slight  trace.  The  urinary  record  is  given 
in  table  40. 


42 


METABOLISM   IN    SEVERE   DIABETES. 


EXPERIMENTS   WITH    CASE    P. 

With  this  subject,  three  bed-calorimeter  experiments  were  made  and  eight 
respiration  experiments;  the  larger  part  of  these  formed  a  part  of  two  series. 
Series  I,  which  was  made  on  September  29,  1911,  consisted  of  three  experi- 
ments, i.e.,  a  respiration  experiment  (P2),  followed  by  an  experiment  with  the 
bed  calorimeter  (P3),  and  concluded  by  a  second  respiration  experiment  (P4). 
Series  II,  which  was  carried  out  October  9-10,  1911,  included  five  experiments, 
beginning  with  a  respiration  experiment  (P5)  with  the  subject  fasting,  which 
was  followed  by  two  oatmeal  experiments,  the  first  with  the  bed  calorimeter 
Table  40. — Clinical  chart — Case  P. 


Date. 

i 

u 

s 

"o 

<0 

B 
"o 

> 

"> 

o 

tc 

g 

Q. 

1 

3 

i 

1 

2 

Ammonia. 

Sugar. 

-a  0 

^^ 

0 

a 
0 

TJ  0 

.2 
0 

0 

1 

J: 
ll 

I§ 

n 
si 

J 

J 
2 
>. 

m 

1911. 
Sept  16-17 

c.c. 

1033 
1030 
1028 
1027 
1026 
1027 
1027 
1025 
1021 
1027 
1025 
1024 
1022 
1034 
1023 
1025 
1026 
1025 
1027 
1026 
1021 
1026 
1034 
1024 
1028 
1026 
1024 
1024 
1026 
1027 
1032 
1029 
1027 
1026 
1022 
1025 
1024 
1022 
1025 

1027 

+ 

+ 
+ 

S1.+ 

+ 
++ 
++ 

++++ 

++++ 

+++ 

++ 

++++ 

0 

+++ 

++++ 

++++ 

++++ 

++++ 

++ 

+++ 

+++ 

++ 

++ 

S1.+ 

++++ 

++++ 

+++ 

+++ 

++++ 

++++ 

+++ 

++++ 

++ 

+++ 

++++ 

+ 

+++++ 

gms. 

n.i 

14.5 

i2;4 

10.9 
5.3 

10.6 
14.4 
18.4 
16.9 
14.9 

13^2 
17.8 
11.1 
8.2 
16.0 
14.2 
14.9 
14.0 
22.4 
17.7 
16.1 
13.6 
19.5 
15.8 
15.4 
22.0 
14.2 

15^2 
17.9 

14.5 

gms. 

i.h 

4.6 

4.4 

i.9 

i'.2 
4.5 

4.4 
2.1 
5.0 
4.1 

4^9 

4.2 
4.7 

p.ct. 

2k'.3 
26.1 

37:6 

32!6 
25.7 

n.i 

23.1 
30.4 

25.2 

24.3 
25.9 

gms. 

144 

'86 
108 

"7.5 

96 

105 

81 

59 

65 

117 

78 

117 

120 

13.8 

163 

48 

99 

54 

79 

95 

115 

114 

114 

112 

116 

84 

127 

141 

91 

127 

149 

116 

77 

119 

97 

106 

gms. 

14.8 

14.0 

14.0 

130 

94 

75 

90 

61 

54 

78 

74 

63 

39 

55 

88 

101 

106 

112 

13.0 

139 

44 

63 

36 

62 

74 

83 

88 

84 

86 

104 

69 

105 

113 

68 

107 

127 

96 

58 

'84 

gms. 

'85 
85 

100 
80 
75 
75 
55 

gms. 

-'45 

-  15 

-  10 

-  35 

-  5 

gms. 
0 
0 
0 
8 
12 
12 
12 
12 
12 
12 
12 
12 
20 
20 
24 
24 
24 
24 
24 
20 
20 
20 
16 
20 
20 
20 
24 
20 
20 
20 
16 
24 
20 
20 
20 
20 
20 
20 
16 
12 
16 

kilos. 
42.1 
42.1 
41.5 
40.9 
40.9 
40.2 
40.8 
41.1 
40.9 
41.3 
40.9 
39.9 
39.7 
39.1 
38.6 
39.5 
40.5 
40.5 
40.8 
40.7 
41.4 
41.1 
40.0 

39.5 
39.5 
39.6 
39.9 
39.1 
39.1 
38.4 
38.9 
39.4 
39.5 
39.4 
39.3 
38.9 
38.9 
39.1 
39.1 
38.4 

Sept.  17-18 

3360+ 

1920+ 

3430 

3360 

2200 

3000 

2780 

2980 

2980 

3090 

2880 

3280 

1840 

3650 

3600 

4080 

4000 

3320+ 

4080 

4360 

4500 

3620 

2835 

3330 

3200 

3680 

3800 

4320 

4000 

2885 

3100 

3520 

3380 

4100 

4520 

3420 

3220 

3720 

3340 

2800 

Sept.  18-19 

Sept   19-20 

Sept.  20-21 

Sept.  21-22 

Sept  22-23 

Sept.  23-24 

Sept  24-25     

45  1-  30 
40   -  55 
40    -  65 

Sept.  25-26  

Sept.  26-27 

Sept.  27-28  

40 

15 

165 

80 
80 
80 
80 
60 
60 
50 
50 
15 

25 

45 
40 
50 
44 
55 
50 
80 
80 
75 
80 
75 
75 
75 

-  40 

-  45 
+100 

-  35 

-'35 

-  40 

-ios 

+    2 

-  50 

-  40 

-'76 

-  70 

-  75 

-  65 

-  70 

-  60 

-  35 

-  45 

-  60 

-  15 

-  45 

-  75 

-  40 

Sept.  28-29= 

Sept.  29-30'.     . 

Sept.  30  to  Oct.  1 

Oct.     1-  2 

Oct.     2-3 

Oct.     3-4 

Oct.     4-5 

Oct.     5-6 

Oct.     6-7 

Oct.     7-8 

Oct.     8-  9 

Oct.     9-10 

Oct.   10-11 

Oct.    11-12 

Oct.    12-13 

Oct.    13-14 

4.5     26.4 
6.5     23.9 
5.5  !  25.6 
5.0     25.5 
4.5  1  27.2 
4.7  1  19.8 
5.3     27  6 

Oct.    14-15 

Oct.    15-16 

Oct.   16-17 

Oct.   17-18 

Oct.    18-19 

Oct.    19-20 

Oct.   20-21 

4.0 

4!i 
4.1 

3  7 

21.4 
23!7 

2i  6 

Oct.   21-22 

Oct.   22-23 

Oct.   23-24 

Oct.   24.25 

Oct.   25-26 

Oct.   26-27.. 

++ 

iPer  cent.  ^  Vegetable  day,  vegetables,  bacon,  broths,  240  c.c.  cream. 

5  Oatmeal  day,  240  gms.  oatmeal,  180  gms.  butter,  240  c.c.  cream. 

(P  6)  and  the  other  vnth.  the  respiration  apparatus  (P  7) .  In  the  fourth  experi- 
ment (P8),  the  subject  spent  the  night  in  the  bed  calorimeter,  and  the  series 
was  concluded  by  a  respiration  experiment  (P9)  following  a  beefsteak  break- 
fast. A  comparison  of  the  data  for  the  calorimeter  experiments  is  given  in 
table  57.     The  vital  statistics  for  this  subject  were  as  follows: 

Date  of  birth,  May  10,  1894;  height,  173  cm.;  range  in  body-weight  with- 
out clothing  during  experiments,  38.7  to  40.9  kilos. 


STATISTICS   OF   EXPERIMENTS. 


43 


Respiration  Experiment  No.  PI. 

Date,  September  25,  1911.     Body-weight  without  clothing,  40.9  kilos. 

On  the  morning  of  the  experiment  the  subject  came  to  the  laboratory, 
fasting,  having  had  only  a  cupful  of  moderately  strong  coffee  at  7  a.  m.  He  lay 
down  upon  the  couch  at  T**  32""  a.  m.;  mosquito  netting  was  thrown  over  his 
face,  shoulders,  and  arms;  his  feet  were  crossed  and  his  arms  folded  upon  his 
chest.     The  experiment  began  at  8^  54™  a.  m.,  continuing  for  three  15-minute 

Table  41. — Results  of  respiration  experiment  No.  PI. 


Date  and  time. 


Sept.  25,  1911: 
'8'' 54™  a.m. 
9    24    a.m. 
9    55    a.m. 

Average . . 


9?"^'?"     '     Oxygen 
Duration.     ,i[Xatd     absorbed 
per  minute.   Pernunute. 


Respiratory 
quotient. 


Average 
pulse-rate. 


mm.  sec. 
15      8 
14    59 
14    56 


c.c. 
164 
144 
145 


c.c. 
215 
214 
215 


0.76 
.67 
.68 


2  151 


2215 


,70 


Average 

respiration 

rate. 


'  Subject  drank  a  cup  of  coffee  (quite  strong)  at  7  a.r 
2  Carbon  dioxide  eliminated  per  kgm.  per  minute,  3. 


CO.;  oxygen  absorbed  per  kgm.  per  minute,  5.26  i 


periods,  with  intermissions  of  14  to  17  minutes.  In  the  first  period  he  un- 
crossed his  feet  at  9^  04*"  a.  m.  In  the  third  period  he  moved  his  arm  to  his 
side,  as  it  felt  cramped.  Aside  from  these  movements,  the  subject  was  quiet 
and  awake  throughout  the  experiment.  Previous  to  the  experiment,  he  uri- 
nated at  7  a.  m.,  and  at  8''  30™  a.m.  he  urinated  and  defecated.  The  results  of 
the^^experiment  are  given  in  tables  41  and  42. 

Table  42. — Statistics  of  urine — Respiration  experiment  No.  PI. 


Date  and  period. 


Volume. 


Sept.  25,  1911: 

17'^  00™  a.m.  to  8'»30™a.m. 
8  30  a.m.  10  14  a.m. 
Sept.  25-26,  1911: 

lO'^  14™  a.m.  to   7**  00™  a.m . 


c.c. 
197 
174 

2610 


Specific 
gravity. 


Total 
nitrogen. 


Sugar. 


1.025 
1.023 


1.029 


gms. 
0.93 

.77 

12.91 


gms. 
5.0 
3.7 

82.9 


'  Subject  drank  a  cup  of  strong  coffee  at  7  a.m. 

Respiration  Experiment  No.  P2. 

Date,  September  29,  1911.     Body-weight  without  clothing,  39.7  kilos. 

This  was  the  initial  experiment  of  Series  I,  and  was  divided  into  two  parts, 
the  first  part  following  a  fast,  and  the  second  following  the  ingestion  of  food. 

The  subject  arrived  at  the  laboratory,  without  breakfast,  at  7*^  40™  a.  m., 
and  lay  down  upon  the  couch  at  7*^  52™  a.  m.  At  8"^  01™  a.  m.  he  drank  a  glass 
of  water.  The  fasting  portion  of  the  experiment  began  at  8**  20™  a.  m.,  con- 
tinued for  three  periods  of  14  to  15  minutes,  and  ended  at  O**  28™  a.  m.  The 
subject  then  ate  375  grams  of  cooked  oatmeal  and  45.5  grams  of  cream,  taking 
at  the  same  time  4  grams  of  sodium  bicarbonate  in  100  c.c.  of  water,  and 
drinking  200  c.c.  of  cold  water.  The  food  was  taken  between  9»'  42™  a.  m.  and 
10^  34™  a.  m.,  although  not  all  at  one  time.  He  urinated  at  9*^  30™  a.  m.,  and  lay 
down  on  the  couch  again  at  lO'^  35™ a.  m.  for  the  final  periods  of  the  experiment; 
four  15-minute  periods  followed,  beginning  at  10^  51™  a.  m.  and  ending  at  1^  04™ 
p.  m.  He  urinated  at  U'^  41™  a.  m.  and  again  at  1''  26™  p.  m.,  after  the  experi- 
ment was  over.  The  mouthpiece  was  used  in  all  of  the  periods,  the  pulse  and 
respiration  rates  being  taken  in  the  usual  manner.     After  the  third  fasting 


44 


METABOLISM   IN   SEVERE   DIABETES. 


period  the  subject  complained  that  his  legs  felt  stiff  from  keeping  still  so  long. 
He  was  awake  and  very  quiet  during  practically  all  of  the  experiment,  save  for 
a  few  slight  movements  of  the  hands  and  feet  which  seemed  to  be  due  to 
nervousness.    The  results  of  the  experiment  are  given  in  tables  43  and  46. 

Table  43. — Results  of  respiration  experiment  No.  P2. 


Date  and  time.         Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

Sept.  29,  1911: 

Without  food— 
S**  20™  a.m. 

8  46    a.m. 

9  13    a.m. 

min.  sec. 
15      0 
14      3 
14    59 

c.c. 
147 
145 
147 

c.c. 
205 
206 
214 

0.72 
.70 
.69 

69 
71 
75 

17 
17 
19 

1146 

177 
162 
162 
157 

1208                  .70 

72 

82 
80 
80 
77 

18 

19 
19 
19 
18 

With  food- 
no'' 51"  a.m. 

11  16    a.m. 

12  22    p.m. 
12    50    p.m. 

14  55 

15  4 
14    57 
14    45 

249 
228 
232 
227 

.71 
.71 
.70 
.69 

3  165 

3  234 

.70 

80 

19 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,  without  food,  3. 63  c.c;  oxygen  absorbed 

per  kilogram  per  minute,  without  food,  5.24  c.c. 
2 Subject  ate  375  gm.s.  cooked  oatmeal  and  45.5  gms.  cream  between  9°  42™  and  9°  55"  a.m.  and 

between  lO''  30™  and  lO''  34™  a.m. 
3Carbon  dioxide  eliminated  per  kilogram  per  minute,  with  food,  4.16  c.c;  oxygen  absorbed  per 

kilogram  per  minute,  with  food,  5.89  c.c. 

Calorimeter  Experiment  No.  P3. 

Date,  September  29,  1911.     Body-weight  without  clothing,  39.7  kilos. 

In  this  experiment,  which  was  the  second  in  Series  I,  the  bed  calorimeter 
was  used  for  the  first  time  with  this  subject.  Food  had  been  taken  during  one 
of  the  intermissions  in  the  respiration  experiment  which  preceded  the  calori- 
meter experiment.  At  1^  12""  p.  m.,  a  meal  consisting  of  241  grams  oatmeal 
and  37  grams  of  cream  was  eaten,  together  with  4  grams  of  sodium  bicarbonate 
taken  in  100  c.c.  of  water.  The  subject  entered  the  bed  calorimeter  at  l^  37™ 
p.  m.  and  the  experiment  began  at  2''  20""  p.  m.  After  two  45-minute  periods, 
the  experiment  ended  at  3''  50™  p.  m.  Both  pneumographs,  also  the  stetho- 
scope, were  used  for  the  regular  records,  but  during  the  last  20  minutes  of  the 
second  period  the  pulse-rate  could  not  be  obtained,  as  the  subject  had  turned 
over  on  his  side.  He  had  boils  on  the  back  of  his  neck,  but  said  after  the  exper- 
iment that  he  was  very  comfortable  in  the  calorimeter,  and,  in  fact,  slept  the 
greater  part  of  the  time.  He  urinated  at  1''  26"'  p.  m.  and  3''  55""  p.  m.  No 
water  was  taken  during  the  experiment.  The  records  of  the  experiment  may 
be  found  in  tables  44  and  46. 

Table  44. — Measurements  of  metabolism — Calorimeter  experiment  No.  PS. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 
minute. 

Total.          f^\ 
mmute. 

Sept.  29.  1911: 

1 2''  20"  p.m.  to  Z^  05"  p.m 

3    05    p.m.       3    50    p.m 

Total  1  hr.  30min 

gms. 
14.0 

c.c. 
n58 

... 

gms. 
14.6 
15.0 

c.c. 
227 
233 

0.70 

73 

70 

18 

17 

29.6 

3  230 

1  Subject  ate  241  gms.  of  cooked  oatmeal  and  37  gms.  of  cream  between  l''  12"  p.m.  and  l*"  24"  p.m. 
a  Carbon  dioxide  eliminated  per  kilogram  per  minute,  2''  20"  to  3''  05"  p.m.,  3.98  c.C; 
•Oxygen  absorbed  per  kilogram  per  minute,  2''  20"  to  3''  50"  p.m.,  5.79  c.c. 


i 


STATISTICS    OF   EXPERIMENTS. 


45 


Respiration  Experiment  No.  P4. 

Date,  September  29.  1911.     Body-weight  without  clothing,  39.7  kilos. 

This  experiment  was  the  third  in  Series  I,  respiration  experiment  P2  and 
calorimeter  experiment  P3  preceding  it.  Immediately  after  the  subject  had 
left  the  bed  calorimeter,  he  ate  114  grams  of  oatmeal  and  10.5  grams  of  cream 
between  4'>  02""  and  4*^  09-"  p.  m.   At  4^  lO"'  p.  m.  he  lay  down  upon  the  couch. 

Table  45. — Results  of  respiration  experiment  No.  P4. 


Date  and  time.         Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

atei'd     R-piratory 
per  minute.     q"°t'ent. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

1 
Sept.  29,  1911:            '    min.  sec. 
14^  se-^p.m....        14    59 
5    03    p.m 1        9    27 

c.c. 
179 
169 

c.c. 
241 

0.74 

78 
82 

19 
19 

Average ' 

2  174 

2  241 

.74 

80 

19 

'Subject  ate  114  gms.  oatmeal  and  10.5  gms.  cream  between  4''  02™  and  4*^  09™  p.m. 

2  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.38  c.c;  oxygen  absorbed  per  kilogram  per  minute,  6.07  c.c. 

At  4^  26™  p.  m.  he  took  4  grams  of  sodium  bicarbonate  in  100  c.c.  of  water. 
The  experiment  began  at  4^  36'"  p.  m.,  continuing  for  two  periods  of  15  and  9 
minutes  respectively,  ending  at  5'>  12'°  p.  m.  He  urinated  at  3''  55'"  p.  m.  and 
5^  35"^  p.  m.  The  mouthpiece  was  used  in  this  experiment,  also,  in  preference 
to  the  nosepiece.  The  subject  was  reported  as  comfortable,  very  quiet,  and 
awake.     The  results  of  the  experiment  are  given  in  tables  45  and  46. 

Table  46. — Statistics  of  urine — -Respiration  experiments  Nos.  P2  and  P4,  and 
calorimeter  experiment  No.  PS. 


Date  and  period. 

Volume. 

Specific 
gravity. 

Total 
nitrogen. 

Sugar. 

Sept.  29,  1911: 

'7*' 00™  a.m.  to    O*"  30™  a.m 

9    30    a.m.       11    41    a.m 

211    41     a.m.         1    26    p.m 

1    26    p.m.         3    55    p.m 

'3    55    p.m.       *5    35    p.m 

c.r. 
257 
255 
308 
365 
265 

1  023 
1.024 
1.026 
1.026 
1,046 

gms. 
0  91 

.78 
.80 
.98 
.67 

gms. 
6.0 
8.4 
11  6 
15  8 
11.0 

1  Subject  ate  375  gms.  of  cooked  oatmeal  and  45.5  gms.  of  cream  and  drank  300  c.c.  of  water  between 

Q^  42™  and  lO*"  34™  a.m. 

2  Subject  ate  241  gms.  of  cooked  oatmeal  and  37  gms.  of  cream  and  drank  100  c.c.  of  water  between 

l*"  12™  and  l*"  24™  p.m. 
'Subject  ate  114  gms.  of  cooked  oatmeal  and  10.5  gms.  of  cream  and  drank  100  c.c.  of  water  between 

4'>  02™  and  4''  09™  p.m. 
<  Subject  ate  107  gms.  of  cooked  oatmeal  and  18.5  gms.  of  cream  between  5*^  30"°  and  5*'  34™  p.m. 

Respiration  Experiment  No.  P5. 

Date,  October  9,  1911.     Body-weight  without  clothing,  40  kilos. 

This  was  the  initial  experiment  in  Series  II.  The  subject  fasted  during 
the  experiment,  having  taken  no  food  for  at  least  12  hours  preceding  it.  He 
came  to  the  laboratory  at  7''  45'"  a.  m.,  lay  down  upon  the  couch  at  7''  50™  a.  m., 
and  the  experiment  began  at  8''  11"'  a.  m.,  continuing  for  two  15-minute  periods. 
The  mouthpiece  and  noseclip  were  used  instead  of  the  nosepieces.  The  room 
was  very  warm  before  the  experiment  began,  but  by  opening  the  windows  a 
little  the  temperature  was  gradually  lowered.  Throughout  the  two  periods 
the  subject  was  very  quiet.  After  it  was  over  he  complained  that  his  mouth 
was  dry  and  that  he  felt  weak.  He  also  said  that  his  stomach  was  out  of  order 
and  he  was  troubled  by  gas,  but  felt  hungry.  The  records  of  the  experiment 
are  given  in  tables  47  and  52. 


46 


METABOLISM    IN    SEVERE    DIABETES. 


Table  47. — Results  of  respiration  experiment  No.  P5. 


Date  and  time.         Duration. 

1 
1 

Carbon 

dioxide 

eliminated 

per  minute. 

per  minute.     q"°tient. 

Averaee    1    Average 
puirrre.l-P-t.on 

Oct.  9,  1911:               ;    min.  sec. 

SlMl-^a-m 15      4 

8    37    a.m 15      S 

C.C.         i           c.c. 

148        '          219                0.68 

145        1          212        {          .68 

71                    17 

77                  18 

Average ' 

'147               '216                 .68        j         74                  18 

1 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.67  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  5.40  c.c. 

Calorimeter  Experiment  No.  P6. 

Date,  October  9,  1911.     Body-weight  without  clothing,  40  kilos. 

This  experiment  was  the  second  in  Series  II,  following  the  fasting  experi- 
ment P5  with  the  respiration  apparatus.  Between  9''  15"*  a.  m.  and  9^  35"" 
a.  m.  the  subject  ate  355.7  grams  of  oatmeal,  52.1  grams  of  butter,  and  49.3 
grams  of  cream.  He  defecated  at  9''  18™  a.  m.  Before  entering  the  bed  calori- 
meter the  subject  also  took  4  grams  of  sodium  bicarbonate  in  about  150  c.c,  of 
water.  The  stethoscope  and  pneumographs  were  used,  but  considerable  diffi- 
culty was  found  in  adjusting  the  stethoscope  properly.  He  entered  the  appa- 
ratus at  9''  50*"  a.  m.,  and  the  experiment  began  at  10''  59""  a.  m.,  continuing 
for  two  45-minute  periods,  one  59-minute  period,  and  one  36-minute  period. 
During  the  third  period  he  urinated  at  1''15'"  p.m.  After  the  experiment  the 
subject  said  he  had  been  very  comfortable  throughout  the  whole  time  and  had 
slept  the  greater  part  of  the  experiment.  His  statement  was  borne  out  by  the 
records  of  the  changes  in  the  temperature  of  the  calorimeter,  for  he  was  very 
quiet  nearly  all  of  the  time.  The  measurements  taken  during  the  experiment 
are  given  in  tables  48  and  52. 

Table  48. — Measurements  of  metabolism — CaloHmeter  experiment  No.  P  G 


Carbon  dioxide 
eliminated. 

Oxygen 

absorbed. 

Respi- 

Average 

Average 

Diite  and  peri 

od. 

ratory 

pulse- 

respira- 

, 

Total. 

Per 
minute. 

Total. 

Per 
minute. 

quotient. 

rate. 

tion  rate. 

Oct 

9.  1911 

1 

•      gms. 

c.c. 

gms. 

c.c. 

W^b^ 

a.m. 

to  111" 

44" 

a 

m.... 

15.5 

174 

16.1 

250 

0.70 

77 

18 

11    44 

a.m. 

12 

29 

P 

m  . .. 

13.7 

156 

12.7 

198 

.79 

79 

18 

12    29 

p.m. 

1 

28 

P 

m 

18.4 

158 

20.3 

242 

.66 

81 

17 

1    28    p.m. 
Total  3  hrs 

2 
5  mir 

04 

P 

111  .  .  . 

11.5 

163 

9.4 

j        183 

.89 

78 

19 

.1      59.1 

163 

58.5 

221 

'  Subject  ate  355.7  gms.  of  cooked  oatmeal,  52.1  gms.  of  butter,  and  49.3  gms.  of  cream  between  9**  15°*  and  9''  So""  a.m. 
-Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.08  c.c;  oxygen  absorbed  per  kilogram  per  minute,  5.53  c.c. 

Respiration  Experiment  No.  P7. 

Date,  October  9,  1911.     Body-weight  without  clothing,  40  kilos. 

This  experiment,  which  was  the  third  in  Series  II,  was  divided  into  two 
parts,  the  subject  taking  food  previous  to  the  first  and  the  fifth  periods.  After 
experiment  P6  was  over,  and  the  subject  had  left  the  bed  calorimeter,  he  ate 
between  2''10'"  p.m.  and  2^23""  p.m., 297  grams  of  oatmeal, 46  grams  of  cream, 
and  44  grams  of  butter.  He  also  took  4  grams  of  sodium  bicarbonate  in  about 
100  c.c.  of  water,  and  drank  200  c.c.  of  water  in  addition.  At  2^  28-"  p.  m.  he 
lay  down  upon  the  couch,  and  the  mouthpiece  and  noseclips  were  adjusted. 
The  first  part  of  the  experiment  began  at  2^  36"^  p.  m.,  continued  for  four 


STATISTICS    OF   EXPERIMENTS. 


47 


periods,  each  from  10  to  15  minutes  in  length,  and  ended  at  5''  05'"  p.  m.  In  the 
first  and  second  periods  the  subject  thought  there  was  a  sUght  leak  about  the 
noseclip,  especially  during  one  of  three  long  breaths  taken  in  the  second  period. 
He  was  very  quiet  in  these  two  periods,  except  for  adjusting  the  noseclip  in  the 
first  minute  of  the  first  period.  Between  the  second  and  third  periods  he  sat 
up  between  3^  09™  and  3''  37""  p.  m.,  and  drank  200  c.c.  of  water  at  3''  lO'"  p.  m. 
He  also  drank  100  c.c.  of  water  between  the  third  and  fourth  periods,  at 4''  47°' 
p.  m.  In  this  intermission  he  slept  most  of  the  time.  At  the  close  of  the  fourth 
period  he  had  a  slight  headache. 

Before  the  second  part  of  the  experiment,  the  subject  ate  at  5''  40'^''  p.  m. 
141.1  grams  of  oatmeal,  10.9  grams  of  butter,  and  23.4  grams  of  cream.  He 
also  drank  100  c.c.  of  water.  At  6  p.  m.  he  defecated,  and  at  6''  lO'"  p.  m.  he 
took  4  grams  of  sodium  bicarbonate  in  100  c.c.  of  water.  At  6^  15™  p.  m.  he 
drank  200  c.c.  of  water.  He  lay  clown  upon  the  couch  again  at  6''  26™  p.  m., 
and  four  additional  15-minute  periods  followed,  the  first  beginning  at  6''  44™ 
p.  m.,  and  the  fourth  ending  at  9'*  40™  p.  m.  Between  the  fifth  and  sixth 
periods  he  sat  up,  but  lay  down  again  at  7''  31™  p.m.  In  the  intermission 
between  the  sixth  and  seventh  periods,  he  urinated  at  8''  03™  p.  m.,  and  also 
drank  100  c.c.  of  water.  During  this  period  he  expressed  himself  as  being 
quite  tired,  and  lay  down  at  8''  30™  p.  m.  In  the  seventh  period  he  was  very 
quiet  and  awake,  taking  several  long  breaths  near  the  end.  He  was  reported 
as  tired  in  the  last  period,  also,  and  very  quiet  and  awake.  After  the  experi- 
ment was  over  he  urinated  and  defecated  at  9**  50™  p.  m.  The  records  of  the 
experiment  are  given  in  tables  49  and  52. 

Table  49. — Results  of  respiration  experiment  No.  P7. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average    '    Average 
pulle%a?e.    ^P^*-" 

Oct.  9.1911: 

12'' 36°' p.m.... 

2    53    p.m 

23    56    p.m 

4    50    p.m.... 

Average 

tnin.  sec. 
10    13 
15      8 
14    55 

14    48 

c.c 
181 
165 
162 
169 

c.c. 
243 
243 

245 
232 

0.74 
.68 
.66 
.73 

83  19 
88                   20 

84  20 
86                   20 

1        3169 

3  241                  .70 

85          1          20 

4  e'^  44™  p.m.... 

7  46    p.m 

8  47    p.m 

9  25    p.m.... 

14    49 

14  59 

15  3 
14    59 

172 
161 
154 
153 

247                  .70 
262                  .62 
230                  .67 
230                  .67 

74                    19 
73                   20 
73                   20 
80                   21 

5  160 

6  242                  .67 

75                  20 

1  Oatmeal,  297  gms.,  butter,  43.6  gms.,  and  cream,  45.7  gms.,  were  eaten  between  2"^  lO""  and  2'^  23™  p.m. 

-  Subject  slept  most  of  the  time  between  this  and  the  following  period. 

3  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.23  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  6.03  c.c. 

••  Oatmeal,  141.1  gms.,  butter,  10.9  gms.,  and  cream,  23.4  gms.,  were  eaten  between  5''  40"'  and  Ob  15""  p.m. 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4  c.c;  oxygen  absorbed  per  kilogram  per  minute,  6.05  c.c. 

Calorimeter  Experiment  No.  P8. 

Date,  October  9-10,  1911.     Body-weight  without  clothing,  40  kilos. 

In  this  experiment,  which  was  the  fourth  of  Series  II,  the  subject  spent  the 
night  in  the  bed  calorimeter.  When  the  subject  entered  the  apparatus  at 
10''  15™  p.  m.,  he  was  dressed  in  pajamas  and  socks,  and  two  pillows  and  two 
blankets  were  given  him.  The  stethoscope  and  the  pneumograph  about  the 
chest  were  not  used,  but  onlj'-  the  pneumograph  about  the  thighs  to  obtain  a 
record  of  the  muscular  movements.  The  measurements  of  the  metabolism 
began  at  11*^49™  p.  m.,  October  9,  and  continued  for  six  periods  of  varying 
length,  ending  at  7''  41™  a. m.,  October  10.  The  subject  was  reported  as  having 
moved  in  the  fourth  period;  in  the  fifth  period  he  moved  about,  telephoned, 


48 


METABOLISM   IN    SEVERE   DIABETES. 


urinated  at  S*"  48™  a.  m.,  and  drank  84  c.c.  of  water  at  about  5''  30"  a.  m.  When 
telephoning  he  reported  himself  as  feeling  well.  After  the  experiment  was 
over  he  urinated  again  at  T''  52°^  a.  m.  The  measurements  made  are  given  in 
tables  50  and  52. 

Table  50. — Measurements  of  metabolism — Calorimeter  experiment  No.  P  8. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Total. 

Per 

minute. 

Total 

Per 

minute. 

Oct.  9  and  10,  1911: 

1  n^  49™  p.m.  to  12h  49™  a.m 

12    49    a.m.         1    49    a.m 

1  49    a.m.         2    49    a.m 

2  49    a.m.        4    27    a.m 

4    27    a.m.         6    40    a.m 

6    40    a.m.         7    41    a.m 

gms. 
15.9 
16.5 
16.3 

27.7 
38.7 
18.2 

c.c. 
135 
140 
138 
144 
148 
152 

gms. 
17.0 
18.5 
17.3 
28.1 
41.0 
18.4 

c.c. 
198 
216 
202 
201 
216 
211 

0.68 
.65 
.68 
.72 
.69 
.72 

Total  7  hra.  52  min.2 

133.3 

144 

140.3 

208 

1  Subject  ate  oatmeal,  butter,  and  cream  between  5^  40™  and  &^  15™  p.m. 

2  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.60  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  5.20  c.c. 

Respiration  Experiment  No.  P9. 

Date,  October  10,  1911.     Body-weight  without  clothing,  38.7  kilos. 

Previous  to  this  experiment,  which  concluded  Series  II,  the  subject  ate  a 
breakfast  between  8*'  IS'"  a.  m.  and  8''  30"^  a.  m.,  consisting  of  168.9  grams  of 
beefsteak,  16  grams  of  butter,  and  2  small  onions,  sliced  and  fried  crisp.  He 
also  took  4  grams  of  sodium  bicarbonate  in  100  c.c.  of  water,  and  drank  in  addi- 
tion 250  c.c.  of  water.  At  8''  35"  a.  m.  he  lay  down  upon  the  couch;  the  experi- 
ment began  at  9''  05™  a.  m.,  and  continued  for  four  15-minute  periods,  ending  at 
12''  10™  p.  in.  In  all  of  the  periods  the  subject  was  very  quiet,  except  for  slight 
movements  of  the  hands  and  feet.  Between  the  first  and  second  periods  the 
subject  lay  upon  the  couch  and  read  a  newspaper;  between  the  second  and  third 
periods  he  sat  up,  but  lay  down  again  about  15  minutes  before  the  next  period 
began;  during  the  intermission  between  the  third  and  fourth  periods  the  subject 
slept.  He  urinated  at  10'' 30™  a.  m.  and  again  at  12''  12™  p.  m.  During  the 
experiment  he  drank  water  only  once,  120  c.c.  at  10''  30™  a.  m.  The  records 
of  the  experiment  are  given  in  tables  51  and  52. 

Table  51. — Results  of  respiration  experiment  N^o.  P9. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 

absorbed 

per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate . 

Average 

respiration 

rate. 

Oct.  10,  1911: 

i9h0.5™a.m 

9    57    a.m 

10  59    a.m 

11  55    a.m 

Average 

ir,in.  sec. 
14    54 
14    52 
14    42 
14    59 

c.c. 
158 
166 
169 
172 

c.c. 
243 
244 
248 
241 

0.65 
.68 
.68 
.71 

77 
79 

81 
85 

19 
20 
19 
19 

=166 

2244        1          .68 

81 

19 

1  Subject  ate  168.9  gms.  beefsteak,  IS  gms.  butter,  and  2  small  onions  between  S^  15™  and  S^  30™  a.m. 

2  Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.29  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  6.30  c.c. 

Respiration  Experiment  No.  PIO. 

Date,  October  16,  1911.     Body-weight  without  clothing,  39.1  kilos. 
This  experiment  was  divided  into  two  sections.     The  first  three  periods 
were  fasting,  no  food  having  been  taken  since  the  evening  meal  of  the  day 


STATISTICS   OF   EXPERIMENTS. 


49 


before,  with  the  exception  of  60  c.c.  of  black  coffee  at  8  a.  m.  The  last  five 
periods  followed  the  ingestion  of  food.  The  subject  had  a  slight  cold  on  the 
day  of  the  experiment. 

Table  52. — Statistics  of  urine — Respiration  experiments  Nos.  Po  to  P9  and 
calorimeter  experiments  Nos.  P  6  and  P8. 


Date  and  period. 

Volume. 

Specific          Total            <,     „, 
gravity.        nitrogen.          ougar. 

Oct.  9,  1911: 

i7hOO™a.m.  to  9h  13™  a.m 

9    13    a.m.       1    15    p.m 

2  1    15    p.m.       2    12    p.m 

2    12    p.m.       5    06    p.m 

5    06    p.m.       8    03    p.m 

8    03    p.m.       9    50    p.m 

Oct.  9-10,  1911: 

39l>  50™  p.m.  to  511  48™  a.m 

Oct.  10,  1911: 

5h  4811  a.m.  to    7^  52™  a.m 

«7    52    a.m.       10    30    a.m 

10    30    a.m.       12    12    p.m 

Oct.  10-11,  1911: 

12h  12™  p.m.  to    7l>  00™  a.m 

c.c. 
280 
480 
144 
460 
373 
256 

610 

232 
350 
270 

2760 

gms. 
1.020              0.92 
1.023              1.41 
1.023                .42 
1.025              1.18 

1.023  .84 
1.025                .64 

1.024  i        2.13 

1.027                .84 
1.019       ;         1.00 
1.022      1        1.01 

!      14.11 

1 

gms. 

5.2 
14.6 

4.5 
14.4 
12.2 

6.9 

12.8 

6  1 
8.6 
7.6 

79.8 

1  Subject  ate  355.7  gms.  cooked  oatmeal,  49.3  gms.  cream,  and  52.1  gms.  butter  between 

gb  15m  and  9b  35™  a.m.,  and  drank  150  c.c.  water  at  10  a.m. 

2  Subject  ate  297  gms.  cooked  oatmeal,  45.7  gms.  cream,  and  43.6  gms.  butter,  and  drank 

300  c.c.  of  water  between  2l>  10™  and  2h  23™  p.m. 
'Subject  ate  141.1  gms.  cooked  oatmeal,  23.4  gms.  cream,  and  10.9  gms.  of  butter,  and 

drank  400  c.c.  of  water  between  5^  40"'  and  6^  15™  p.m. 
*  Subject  ate  168.9  gms.  beefsteak,  16  gms.  butter,  and  2  small  onions,  and  drank  350  c.c. 

water  between  8^  15™  and  8^  30"'  a.m. 

As  usual  with  this  subject,  the  mouthpiece  and  noseclip  were  substituted 
for  the  nosepieces.  Both  pneumographs  were  used,  also  the  stethoscope.  The 
subject  lay  down  upon  the  couch  at  8''  17™  a.  m.  The  experiment  began  at 
8^  48™  a.  m.,  continued  for  three  periods  12  to  15  minutes  in  length  which  ended 
at  9^  48™  a.  m.  The  subject  then  ate  301.5  grams  of  beefsteak  and  20.8  grams 
of  butter,  finishing  at  10''  10™  a.  m.     He  drank  with  the  food  600  c.c.  of  water 

Table  53. — Results  of  respiration  experiment  No.  P 10. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

Oct.  16,  1911: 
Without  food. 

i8h48™a.m.... 

9    11    a.m 

9    36    a.m 

min.  sec. 

14  55 

15  3 
11    35 

c.c. 
159 
154 
152 

c.c. 
221 
217 
219 

0.72 
.71 
.69 

75 

77 
77 

17 
19 
19 

2  155 

164 
166 
178 
169 
181 

2219 

241 
247 
260 
257 
256 

.71 

.68 
.67 
.68 
.66 
.71 

76 

79 
82 
83 
81 
88 

18 

19 
19 
19 
17 
20 

With  food. 

nob  38™  a.m.... 

11  28    a.m.... 

12  22    p.m.... 

1    00    p.m 

1    31    p.m.... 

15      0 

15      7 
14    44 

14  43 

15  3 

M72               *252 

.68 

83         1         19          1 

1 

'Subject  drank  60  c.c.  of  black  coffee  at  8  a.m. 

^Carbon  dioxide  eliminated  per  kilogram  per  minute,  without  food,  3.96  c.c;  oxygen  absorbed  per 
kilogram  per  minute,  without  food,  5.60  c.c. 

3  Subject  ate  301  5  gms  beefsteak  and  20.8  gms.  butter  between  9b  53™  and  10b  lo™  a.m. 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,  with  food,  4.40  c.c;  oxygen  absorbed  per  kilo- 
gram per  minute,  with  food,  6.45  c.c. 

and  took  4  grams  of  sodium  bicarbonate  in  about  100  c.c.  of  water.  The  next 
period  began  at  10**  38™  a.  m.,  the  five  15-minute  periods  ending  at  I''  40™  p.  m. 
The  subject  was  very  quiet  throughout  the  experiment,  only  slight  movements 
being  reported.     During  the  last  three  periods  he  said  he  felt  rather  tired;  in 


50 


METABOLISM   IN    SEVERE   DIABETES. 


the  seventh  period  he  was  sleepy,  and  the  observer  thought  the  hps  dropped 
away  from  the  mouthpiece  and  that  the  subject  fell  asleep  once.  He  was 
awake  in  the  last  period,  however.  In  the  intermission  between  the  fourth 
and  fifth  periods  he  lay  upon  the  couch  reading  a  newspaper.  Between  the 
sixth  and  seventh  periods  he  left  the  room  to  telephone,  and  lay  on  the  couch 
only  about  5  minutes  before  the  next  period  began.  Between  the  seventh  and 
eighth  periods  he  stood  up  and  took  some  water.  In  addition  to  the  water 
taken  with  the  food  he  drank  one  glassful  at  8.25  a.  m.,  100  c.c.  at  12^  44'"  p.  m., 
and  100  c.c.  at  1"^  25'°  p.m.  He  urinated  at  7  a.m.,  9"^  50"^  a.m.,  12'^  ll'"  p.  m., 
and  I*'  48'"  p.  m.     The  records  of  the  experiment  are  given  in  tables  53  and  54. 

Table  54. — Statistics  of  urine — Respiration  experiment  No.  PIO. 


Date  and  period. 


Oct.  16,  1911: 

i7*'00">a.in.  to    g'' 50™ 

=  9    50    a.m.       12    11     p.m. 

12    11    p.m.         1    48    p.m. 
Oct.  16-17,  1911: 

Ih48-Dp.m.  to    7'' 00™  a.m. 


Volume.     1^ 


c.c. 
352 
282 
210 

2040 


1.024 
1.025 
1.025 


Total 
nitrogen. 


gms. 
1.82 
1.54 
1.28 

11.49 


Sugar. 


6.2 
4.9 


59.3 


■  Subject  drank  60  c.c.  of  black  coffee  at  8  a.m.  and  200  c.c.  of  water  at  8*^  25™  a.m. 
2  Subject  ate  301.5  ems.  of  beefsteak  and  20.8  gms.  of  butter  and  drank  700  c.c.  of 
water  between  9'>  53™  a.m.  and  lO*"  25™  a.m. 

Respiration  Experiment  No.  Pll. 

Date,  October  25,  1911.     Body-weight  without  clothing,  39.1  kilos. 

This  experiment  was  similar  to  the  preceding  experiment  in  that  it  was 
divided  into  two  parts,  the  subject  fasting  in  the  first  three  periods,  and  the 
last  periods  following  the  taking  of  food.  The  mouthpiece  and  noseclips 
were  used  instead  of  the  nosepieces.  On  the  morning  of  the  experiment,  the 
subject  came  to  the  laboratory  without  breakfast,  and  lay  down  upon  the 
couch  aXl^  35"*  a.  m.     The  first  three  15-minute  periods  began  at  7^  59™  a.  m., 

Table  55. — Results  of  respiration  experiment  No.  Pll. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory    Average    Lj^of/a^tfon 
quotient,      pulse-rate.  |       ^ate! 

Oct.  25,  1911: 

Without  food— 

7^59™  a.m.... 
8    26    a.m.... 
8    49    a.m 

min.   sec. 

15      0 
15      5 
14    59 

c.c. 

145 
146 
147 

c.c. 

201 
202 
210 

0.72                 66                  17 
.72        i          69                   18 
.70        1         71          j         19 

1146 

149 
160 
194 
172 

1204 

244 
243 
265 
244 

.71                 69         1          18 

With  food— 

lO''  10™a.m2.... 

11  16    a.m.... 

12  32    p.m.... 
1    31    p.m 

14    56 

14  56 

15  15 
15      2 

.61 
.66 
.73 
.70 

74         ,         16 
74          ;          19 
76          !          19 

74          !          18 

'169 

3  249 

.68 

75 

18 

1  Carbon  dioxide  eliminated  per  kgm.  per  minute,  without  food,  3.73  c.c;  o.xygen  absorbed  per  kgm.  per 

minute,  without  food,  5.22  c.c. 
^Subject  ate  284.5  gms.  beefsteak,  23.3  gms.  butter,  and  2  small  onions  between  9°  24™  and  9°  41™  a.m. 
'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  with  food,  4.32  c.c;  oxygen  absorbed  per  kilogram 

per  minute,  with  food,  6.37  c.c. 

and  ended  at  9''  04"^  a.  m.  The  subject  then  ate,  between  9.24  and  9.41  a.  m., 
284.5  grams  of  beefsteak,  23.3  grams  of  butter,  and  two  small  onions,  fried. 
He  also  took  4  grams  of  sodium  bicarbonate  in  100  c.c.  of  water.  After  eating, 
he  lay  down  upon  the  couch  at  9''  43'"  a.  m.,  and  the  four  succeeding  periods 
began  at  10^  10""  a.  m.,  ending  at  I''  46'"  p.  m.     He  was  very  quiet  and  awake 


STATISTICS   OF   EXPERIMENTS. 


51 


throughout  all  of  the  periods.  Several  slight  motions  were  reported  by  the 
observer.  The  third  period  seemed  very  long  to  the  subject.  He  was  sleepy 
in  the  period  directly  following  the  taking  of  food,  but  did  not  go  to  sleep.  In 
the  intermission  between  the  sixth  and  seventh  periods  he  sat  up  for  a  time  and 


Table  56. — Statistics  of  urine- 

-Respiration  experiment  No.  Pll. 

Date  and  period. 

Volume. 

Specific 
gravity. 

Total 
nitrogen. 

Sugar. 

Oct.  25, 1911: 

7h  00"  a.m.  to  lO"^  50™  a.m.'. . . . 

10    .50    a.m.         1    00    p.m 

1    00    p.m.         2    45    p.m 

Oct.  25-26,  1911: 

2h  45""  p.m.  to    7"^  00™  a.m 

c.c. 
476 
390 
276 

2200 

1.022 
1.023 
1.024 

1.024 

gms. 
1.96 
1.75 
1.56 

12.54 

gms. 
11.6 
10.4 
6.9 

67.8 

'Subject  ate  284.5  gms.  beefsteak,  23.3  gms.  butter,  and  2  small  onions,  and  drank 
500  c.c.  water  between  9'^  24™  and  9°  55™  a.m. 

said  he  felt  quite  tired.  In  this  intermission,  also,  he  drank  a  glass  of  water 
containing  4  grams  of  sodium  bicarbonate.  The  subject  urinated  at  7  a.  m., 
10*'  50'"  a.  m.,  1  p.  m.,  and  2''  45™  p.  m.  The  records  of  the  experiment  are 
given  in  tables  55  and  56. 

Table  57. — Comparison  of  metabolism  experiments  in  bed  calormeler  with  Case  P. 
EXPERIMENT  WITHOUT  FOOD. 


Experi- 
ment 
No. 

Date. 

Weight 

of 
subject. 

Length 
of  ex- 
periment. 

Per  minute. 

Respi- 
ratory 
quotient. 

Average 

pulse 

per 

minute. 

Average 
respira- 
tion per 
minute. 

Carbon 
dioxide 
elimi- 
nated. 

Oxygen 
absorbed. 

PS 

1911. 
Oct.  9-10 ». 

kilos. 
40.0 

hrs.  min. 
7    52 

c.c. 
144 

c.c. 
208 

0.69 

EXPERIMENTS  WITH  FOOD. 

P3 
P6 

1911. 
Sept.  29  2. . 
Oct.     9*.. 

Mlos. 
39.7 
40.0 

hrs.  min. 
1    30 
3    05 

c.c. 

3  158 

163 

c.c. 
230 
221 

30.70 
.73 

72 
79 

17.5 
18.0 

'  About  6  hours  before  the  beginning  of  the  experiment  the  subject  ate  141 . 1  gms.  cooked  oatmeal ,  23 .4  gms . 

cream,  and  10.9  gms.  butter. 
2  About  1  hour  before  beginning  of  experiment  the  subject  ate  241  gms.  cooked  oatmeal  and  37  gms.  cream. 
'The  carbon  dioxide  eliminated  and  the  respiratory  quotient  for  this  experiment  are  for  the  period 

2b  20™  to  3^  05™  p.m. 
^Aboutlhour  30  minutes  before  the  experiment  began  the  subject  ate  355.7  gms.  cooked  oatmeal,  52.1 

gms.  butter,  and  49.3  gms.  cream. 

CASE  Q. 
DESCRIPTION    OF   THE    CASE. 

Male;  born  March  1,  1896;  single;  no  occupation;  developed  symptoms  of 
diabetes  at  the  age  of  13,  September  1909;  came  under  our  observation  Novem- 
ber 1910;  diagnosed  as  diabetes  January  1910;  died  in  coma  March  14,  1911. 

Family  history. — No  history  of  diabetes  in  the  family.  Father,  mother, 
and  one  brother  well. 

Past  history. — Greatest  weight,  54.0  kilos,  without  clothes;  weight  Novem- 
ber 13,  1910,  51.6  kilos,  without  clothes.  Measles,  mumps,  whooping-cough, 
severe  tonsilitis  in  1907. 

General  history  of  the  case. — Symptoms  of  diabetes  were  first  observed  in 
September  1909.  A  single  specimen  of  urine  voided  on  rising  in  August  1909 
was  free  from  sugar.  In  November  1909  a  sticky  deposit  was  observed  about 
the  urinal,  but  diabetes  was  not  proved  present  until  January  1910.     The  con- 


52 


METABOLISM   IN    SEVERE   DIABETES. 


dition  of  the  patient  while  at  the  hospital  in  November  1910  was  critical. 
From  December  28,  1910,  to  March  1,  1911,  he  was  under  the  care  of  Dr.  A.  J. 
Hodgson,  at  Waukesha,  Wisconsin,  where  he  gained  in  weight  up  to  54.9  kilos, 
without  clothing.  The  treatment  was  said  to  have  consisted  of  a  large  quan- 
tity of  vegetables,  nuts,  and  water.  Unfortunately  no  analysis  of  a  specimen 
of  the  24-hour  quantity  of  urine  was  made  during  this  period.  Death  occurred 
in  coma  March  14,  1911.  An  examination  of  the  organs  of  the  patient  was 
made  by  Prof.  F.  B.  Mallory,  of  the  Harvard  Medical  School,  who  writes  that 
it  showed  absolutely  nothing  abnormal;  the  pancreas  was  in  all  respects  normal. 

Physical  examination. — A  well-developed  and  nourished  boy  with  good 
color.  Height  168  cm.  Pupils  equal  and  reacted  to  light.  Knee-jerks  nor- 
mal. No  edema.  High-arched  palate.  Pulse-rate  96.  Physical  examina- 
tion was  otherwise  negative  in  September  1910. 

Urine  data. — The  urinary  record  is  given  in  table  58.  Previous  to  Novem- 
ber 1910,  when  the  patient  first  came  under  observation,  the  greatest  quantity 
of  urine  was  3000  c.c.  It  subsequently  rose  to  3500  c.c.  on  December  15,  1910, 
but  after  that  date  there  is  no  accurate  record.  The  reaction  of  the  urine  was 
acid  during  this  period.  The  ammonia  reached  6.4  grams  on  December  15, 
1910,  and  on  November  18-19,  1910,  the  quantity  of  |8-oxybutyric  acid  was  30 
grams.  The  albumen  never  exceeded  a  very  slight  trace.  During  the  summer 
of  1910,  the  patient  was  sugar-free  for  several  months.  Throughout  the  period 
of  observation,  20  grams  of  sodium  bicarbonate  were  given  the  patient  each  day. 


Table  58. — Clinical  chart — Case  Q 

. 

^ 

Ammonia. 

Sugar. 

a 

i 

^ 

a 
1 

1 

•6 

o 

'5 

•a  <u 

s 

°-S 

§ 

Date. 

o 

3 

s 

^i^ 

^•^ 

^ 

>.^ 

J-  =1 

^"3 

_3 

S 

1 

1 

.1 

■3 
0 

1  - 

3 

2 

i 

S 

0 
.a 

> 

zo 

b 

oi 

2 

H 

:^H 

«*" 

« 

0 

0 

« 

1910. 

C.C. 

gtns. 

gms. 

gms. 

p.ct. 

gms. 

gms. 

gms. 

gms. 

kilos. 

Nov.  12-13 

'3030 

1036 

+-I-F- 

121 

51.6 

Nov.  13-14 

3090 

1032 

-I-+++ 

20.2 

105 

93 

55 

-50 

52.5 

Nov.  14-15 

3260 

1029 

++ 

18.7 

3.9 

17.2 

75 

55 

-20 

52.1 

Nov.  15-16 

3200 

1032 

-|-++-h 

17.0 

104 

90 

55 

-50 

51.5 

Nov.  16-17 

2200 

1034 

++++ 

.... 

16.6 

4.8 

23.8 

83 

70 

55 

-  3 

61.3 

Nov.  17-18 

2620 

1034 

++++ 

25.4 

18.1 

94 

55 

-40 

51.1 

Nov.  18-19 

2820 

1033 

-I-++ 

30.0 

15.6 

5.2 

27.4 

iii 

96 

55 

-55 

51.6 

Nov.  19-20 

2570 

1027 

-I-++ 

27.5 

14.0 

4.6 

27.0 

67 

51 

55 

-10 

51.4 

Nov.  20-212..,. 

2520 

1029 

+++ 

26.7 

11.2 

4.0 

29.4 

73 

60 

55 

-20 

51.4 

Nov.  21-22  3.... 

1430 

1037 

19.7 

7.0 

3.0 

35.3 

69 

63 

165 

+95 

51.5 

Nov.  22-23*.... 

1565 

1038 

++++ 

19.6 

7.0 

2.2 

25.9 

92 

81 

165 

+75 

Nov.  23-24  5. . . . 

. 

Nov.  24-25 

2250 

1033 

+ 

12.3 

90 

81 

20 

-70 

Nov.  25-26 

3500 

1030 

+++ 

13.7 

117 

105 

Dec.  14-15 

3500 

1035 

++ 

6.4 

140 

'For  20  hours.  2  Vegetable  day;  vegetables,  6  eggs,  240  c.c.  cream,  bacon,  coffee,  broths. 

'For24^hrs.;  oatmeal  day.        'Oatmeal  day.  ^For  record  of  urine  for  Nov.  23-24,  see  table  63. 

<  NaHCOa  given  each  day,  20  gms. 

EXPERIMENTS   WITH   CASE    Q. 

Four  calorimeter  experiments  were  made  with  this  subject,  all  with  the 
bed  calorimeter.  In  the  first  and  fourth  experiments,  the  metabolism  after  a 
12-hour  fast  was  studied,  and  in  the  second  and  third  experiments,  after  the 
ingestion  of  oatmeal.  A  comparison  of  the  results  of  these  experiments  is 
made  in  table  64.  There  were  no  respiration  experiments  with  this  subject. 
The  vital  statistics  were  as  follows: 

Date  of  birth,  March  1.  1896;  height,  168  cm. ;  range  in  body-weight  with- 
out clothing  during  experiments,  51.4  to  52.0  kilos. 


STATISTICS    OF   EXPERIMENTS. 


53 


Calorimeter  Experiment  No.  Q1. 

Date,  November  19,  1910;  body-weight  without  clothing,  51.4  kilos. 

The  subject  came  to  the  laboratory  early  in  the  morning  without  break- 
fast and  entered  the  bed  calorimeter  at  y^lO'"  a.  m.  The  experiment  began  at 
8^  09""  a.  m.,  and  continued  for  three  45-minute  periods,  ending  at  10^  24"*  a.  m. 
The  pulse  and  respiration  rates  were  obtained  in  the  usual  way.  Throughout 
the  whole  experiment  the  subject  lay  on  his  back,  reading,  and  was  very  quiet. 
After  the  experiment  was  over  he  said  that  although  he  felt  rather  warm  he  was 
very  comfortable  and  found  his  stay  in  the  chamber  pleasant.  The  records 
of  the  experiment  may  be  found  in  table  59. 

Table  59. — Measurements  of  metabolism — Calorimeter  experiment  No.  Q  1. 


Date  and  period. 

Carbon  dioxide 

eliminated. 

Oxygen  absorbed. 

1    Respi- 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 
minute. 

Total. 

Per        quotient, 
minute,   j 

Nov.  19,  1910: 

8^  09™  a.m.  to    8'^  54™  a.m 

8  54    a.m.         9    39    a.m 

9  39    a.m.       10    24    a.m 

Total  2  hrs.  15  mins.i 

gms. 
16  4 
15.4 
14.9 

c.c. 
184 
174 
169 

g?ns. 
15.5 
15.5 
13.8 

c.c.       1 
241      \      0.77 
241              .72 
216      1        .78 

79 
79 
79 

23 
20 
19 

46.7 

176 

44.8 

232      1       ....       i 

•Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.42  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.51  c.c. 
The  urine  collected  between  e*"  45™  and  10"  4J™  a.m.  amounted  to  270  c.c;  specific  gravity  1.029,  and  contained 
1.75  gms.  nitrogen  and  8  gms.  sugar. 

Calorimeter  Experiment  No.  Q2. 

Date,  November  21,  1910.     Body-weight  without  clothing,  51.5  kilos. 

Previous  to  coming  to  the  laboratory  at  7  a.  m.  the  subject  ate  a  break- 
fast consisting  of  approximately  60  gms.  oatmeal  (weight  uncooked)  and  90 
gms.  cream.  He  entered  the  bed  calorimeter  at  7^20™  a.m.;  the  experiment 
began  at  8''  18™  a.  m.,  and  continued  for  three  45-minute  periods,  ending  at 
10''  33"  a.  m.     The  subject  was  dressed  in  his  ordinary  clothing,  and  lay  on 

Table  60. — Measurements  of  metabolism— Calorimeter  experiment  No.  Q  2. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 

minute. 

Total. 

Per 
minute. 

Nov.  21,  1910: 

'  S*"  18""  a.m.  to    9^  03™  a.m 

9    03    a.m.         9    48    a.m 

9    48    a.m.       10    33    a.m 

Total  2  hrs.  15  min.- 

gms. 
17.6 
17.0 
16.4 

c.c. 
199 
192 
186 

gms. 
14.8 
15.9 
15.9 

c.c. 
230 
248 
247 

0.86 
.78 
.75 

81 
82 
83 

18 
26 
30 

51.0 

192 

46.6 

242 

'Subject   ate  for  breakfast  at   about  G*"  3)™  (?)  a.m.   approximately  60  gms.  oatmeal  (weight  uncooked)  and 

90  gms.  croam. 
^Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.73  c.c  ;  oxygen  absorbed  per  kdogram  per  mmute,  4.70  c.c. 

a  pneumatic  mattress,  with  his  head  resting  upon  two  pillows  and  lifted  to  an 
angle  of  35°  by  means  of  a  wooden  head-rest.  Throughout  the  experiment  he 
lay  very  quiet  on  his  back,  without  reading.  Just  before  entering  the  calorim- 
eter the  subject  drank  water,  but  no  water  was  taken  during  the  experiment. 
He  urinated  at  6*^  50™  a.  m.,  before  coming  to  the  laboratory,  and  again  at 
lO''  51™  a.  m.,  after  the  experiment  was  over.  The  records  are  given  in  tables 
60  and  63. 


54 


METABOLISM   IN    SEVERE    DIABETES. 


Calorimeter  Experiment  No.  Q3. 

Date,  November  22,  1910.     Body-weight  without  clothing,  51.8  kilos. 

This  experiment  also  followed  the  ingestion  of  oatmeal,  the  subject  eating 
a  breakfast  consisting  of  approximately  70  gms.  of  oatmeal  (weight  uncooked), 
15  gms.  butter,  and  60  gms.  cream.  The  subject  reached  the  laboratory  at 
7^  35""  a.  m.,  entered  the  bed  calorimeter  at  1^  46""  a.  m.,  and  the  experiment 
began  at  S*"  26"  a.  m.,  continuing  for  three  45-minute  periods  and  ending  at 
10'*  45""  a.  m.  The  subject  was  very  quiet  during  the  first  two  periods,  and 
was  probably  asleep  during  the  second  period.  At  the  beginning  of  the  third 
period  he  began  reading  and  continued  to  read  until  shortly  before  the  close 
of  the  experiment.  The  subject  urinated  both  before  and  after  the  experi- 
ment, at  1^  20"*  a.  m.  and  ll"*  05™  a.  m.  respectively.  The  records  are  given 
in  tables  61  and  63. 

Table  61. — Measurements  of  metabolism — Calorimeter  experiment  No.  Q  3. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  ab.sorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 

minute. 

Total. 

Per 
minute. 

Nov.  22,  1910: 

1  Sl"  26'"  a.m.  to   9'>  12™  a.m 

9    12    a.m.         9    57    a.m 

9    57    a.m.       10    45    a.m 

Total  2  hrs.  19  min.- 

gmx. 
16.3 
15.9 
16.7 

c.c. 
179 
180 
178 

gms. 
15.5 
14.3 
15.9 

c.c. 
235 
222 
232 

0.76 
.81 
.77 

70 
68 
66 

23 
22 
26 

48.9 

179 

45.7 

230 

'Subject  ate  for  breakfast  at  about  7  (?)  a.m.  approximatelj'  70  gms.  oatmeal  (weight   uncooked),  15  gms. 

butter,  and  60  gms.  cream. 
'Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.46  c.c. :  oxygen  absorbed  per  kilogram  per  minute,  4.44  c.c. 

Calorimeter  Experiment  No.  Q4. 

Date,  November  23;  1910.     Body-weight  without  clothing,  52.0  kilos. 

On  the  morning  of  the  experiment  the  subject  came  to  the  laboratory  with- 
out breakfast  at  7^*  35™  a.  m.,  and  entered  the  bed  calorimeter  at  7^  42™  a.  m. 
The  experiment  began  at  8^  35™  a.  m.,  and  continued  for  three  45-minute 
periods,  ending  at  10'*  50™  a.  m.  Throughout  the  experiment  the  .subject  was 
very  quiet,  not  even  reading.  He  urinated  both  before  and  after  the  experi- 
ment, at  7^  25™  a.  m.  and  ll**  03™  a.  m.,  respectively.  The  records  of  the  experi- 
ment are  given  in  tables  62  and  63. 

Table  62. — Measurements  of  metabolism — Calorimeter  experiment  No.  Q  4- 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

.Average 
respira- 
tion rate. 

Total. 

Per 
minute. 

Total.       ^?fte. 

Nov.  23,  1910: 

8^  35"  a.m.  to    9^  20™  a.m 

9    20    a.m.       10    05    a.m 

10    05    a.m.       10    50    a.m 

Total  2  hrs.  15  min.^ 

gms. 
15.3 
15.7 
14.3 

c.c. 
173 
178 
162 

gms.             c.c. 
13.7              213 
15.3              238 
13.5              210 

0.81 
.75 
.77 

163 
66 
65 

30 
28 
31 

45  3              171       1      i9.  a 

220 

1 

1 

I  One  record  at  9^  18°^  a.m. 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.29  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  4.23  c.c. 


STATISTICS    OF   EXPERIMENTS. 


55 


Table  63. — Statistics  of  urine — Calorimeter  experirnents  Nos.  Q  2-Q  4. 


Date  and  period. 


Nov.  21,  1910:  6^  50™  a.m."  to  lO*"  51™  a.m.  .  . 
Nov.  21-22,  1910:  10*^51™  a.m.  to  7^20™  a.m. 
Nov.  22,  1910:  7"^  20™  a.m.s  to  lll>  0-5™  a.m.. . 
Nov.  22-2.3,  1910:  11^  05™  a.m.  to  7''  25™  a.m. 
Nov.  23,  1910:  7'^  25™  a.m.  to  ll""  03™  a.m .  .  . . 
Nov.  23-24,  1910  ^ 


Specific 

gravity. 

c.c. 

410 

1.035 

1020 

1.038 

327 

1.043 

1240 

1.038 

116 

1.041    1 

1.032    1 

1 

Total 
nitrogen. 


Sugar. 


gms. 
1.93 

i!56 

5.44 

.70 

6.35 


gma. 
27.0 
J40.4 
26.4 
69.3 
7.0 
21.1 


'  Subject  ate  oatmeal  at  about  6''  30™  (?)  a.m.     -Sugar  by  fermentation.    ^Subject  ate  oatmeal  at  about  7  (?)a.m. 
*  Volume  of  urine  analyzed  was  900  c.c.     It  could  not  be  learned  whether  this  was  the  total  for  the  remainder 
of  the  24  hours.    The  nitrogen  and  sugar  for  the  total  24  hours  are,  therefore,  not  known. 

T.\BLE  64. — Comparison  of  metaholism  experiments  in  the  bed  calorimeter  ivith  Case  Q. 
EXPERIMENTS  WITHOUT  FOOD. 


Per  minute. 


Experi- 
ment 
No. 


Date. 


Weight 

of 
subject. 


1910. 
Q  1    I  Nov.  19. 
Q4    I  Nov.  23. 


kilos. 
51.4 
52.0 


Length    | 
of  ex-     ]   Carbon 
periment.    dioxide 
I    elimi- 
nated. 


vim. 
15 
15 


c.c. 
176 
171 


Oxygen 
absorbed. 


Respi- 
ratory 
quotient. 


Average  ;  Average 

pulse      I  respira- 

I   per    tion  per 

minute,   minute. 


c.c. 
232 
220 


0.76 

.78 


20.5 
29.5 


EXPERIMENTS  WITH  FOOD. 


1910. 

kilos. 

hrs. 

min. 

c.c. 

c.c. 

02 

Nov.  2H.. 

51.5 

2 

15 

192 

242 

0.80 

82 

Q3 

Nov.  222.. 

51.8 

2 

19 

179 

230 

.78 

68 

24.5 
23.5 


1  Subject  ate  oatmeal  for  breakfast  about  1  hour  45  (?)  minutes  before  experiment  began. 
-Subject  ate  oatmeal  for  breakfast  about  1  hour  30  minutes  (?)  before  experiment  began. 

CASE  R. 


DESCRIPTION    OF   THE    CASE. 

Male;  born  March  16,  1863;  married;  financier;  developed  symptoms  of 
diabetes  in  November  1903,  but  the  diagnosis  was  not  made  until  March  21, 
1904;  came  under  our  observation  June  27,  1910;  died  of  pulmonary  tuber- 
culosis March  14,  1912. 

Family  history. — No  history  of  diabetes  in  the  family.  Father  well  at  82 ; 
mother  died  of  arterio-sclerosis  at  69.  Three  sisters  and  four  children  well. 
Seven  uncles  died  of  pulmonary  tuberculosis. 

Past  history. — Wiry  but  not  strong.  Measles,  mumps,  Avhooping-cough, 
typhoid,  scarlet  fever,  jaundice  at  approximately  15  years  of  age,  malaria  twice. 

General  history  of  the  case. — The  record  of  the  case  is  given  in  full,  because 
no  patient  has  come  under  our  observation  who  more  carefulh'  carried  out 
modern  dietetic  treatment  and  also  because  of  the  extreme  acidosis  which  dis- 
appeared with  the  onset  of  tuberculosis.  In  November  1903  the  patient  was 
"run  down."  In  January  1904  he  had  polydipsia  and  was  a  trifle  irritable. 
The  urine  of  March  21, 1904,  had  a  specific  gravity  1.041,  vath  a  sugar  content 
of  7.8  per  cent.  Under  dietetic  treatment  sugar  disappeared  from  the  urine  on 
April  15,  1904,  and  did  not  return  until  March  13,  1905,  when  the  diet  was 
somewhat  relaxed.  Later  it  again  disappeared,  not  recurring  until  October  24, 
1905.     It  was  absent  throughout  1906,  and  present  at  only  two  of  15  analyses 


56  METABOLISM   IN    SEVERE   DIABETES. 

during  1907.  On  January  24,  1908,  0.3  per  cent  of  sugar  was  present;  in  April 
of  the  same  year  Prof,  von  Noorden  found  difficulty  in  making  the  urine 
sugar-free  despite  vegetable  days  and  oatmeal  days,  and  following  the  patient's 
visit  to  Vienna  the  sugar  was  invariably  present.  Along  with  the  gradual 
increase  in  acidosis  which  Wiis  first  noted  in  1908,  the  diet  was  gradually 
relaxed,  and  apparently  each  time  with  benefit.  During  the  latter  part  of 
December  1911  tuberculosis  appeared  and  the  weight  fell  rapidly.  With  the 
appearance  of  the  tuberculosis  there  was  a  gradual  increase  in  the  tolerance  for 
carbohydrates  and  a  decrease  in  the  acidosis,  a  condition  similar  to  that  which 
occurred  in  Case  A.  Similar  occurrences  have  been  recorded  by  various  writ- 
ers. All  data  relating  to  the  case  from  the  beginning  of  observation,  June  27, 
1910,  until  death  on  March  14,  1912,  can  be  considered  absolutely  reliable. 

Physical  examination. — Greatest  weight,  66.7  kilos,  without  clothing; 
June  27,  1910,  60.5  kilos,  without  clothing.  Height,  181  cm.  Pupils  equal 
and  reacted  to  light.  Teeth  in  excellent  condition,  undoubtedly  due  in  part 
to  cleansing  by  dentist  every  6  weeks.  Lungs  normal.  Heart,  apex  in  mammil- 
lary  line,  systolic  at  base  and  apex.  Blood-pressure,  126.  Pulse-rate,  96. 
Right  kidnej^  large  and  palpable  throughout.  Liver,  spleen,  and  left  kidney 
not  palpable.     No  note  of  abnormality  of  knee-jerks. 

Uritie  data.- — The  reaction  of  the  urine  was  acid  throughout  the  period  of 
our  observation,  but  according  to  von  Noorden's  records,  it  had  previously 
been  alkaline  several  times.  The  acidosis  was  extreme  from  June  1910  until 
the  last  few  months  of  life.  In  no  other  case  coming  under  our  observation  has 
the  quantit}"  of  jS-oxybutyric  acid  been  greater  than  with  this  patient,  increas- 
ing to  over  50  grams  in  March,  April,  August,  September,  November,  and 
December  1911,  the  amount  on  Christmas  Day  being  54.8  grams.  Although 
the  amount  of  nitrogen  in  the  diet  was  kept  at  a  moderate  level,  the  ammonia 
was  high  from  the  first,  reaching  8  grams  in  February  1911,  notwithstanding  20 
grams  of  sodium  bicarbonate  were  being  taken  daily.  The  quantity  of  sugar 
steadily  rose  from  approximately  50  grams  in  June  1910  up  to  200  grams  in 
March  1911,  but  subsequently^  somewhat  decreased,  falling  far  below  this  in 
the  spring  of  1912,  coincident  with  the  presence  of  tuberculosis.  A  minus  car- 
bohydrate balance  was  present  from  June  1910  until  the  last  two  months  of 
life.  The  body-weight  slowly  fell  from  60.5  kilos,  on  June  29,  1910,  to  34.5 
kilos,  on  March  23,  1912.     The  urinary  record  is  given  in  table  65. 

EXPERIMENTS   WITH    CASE    R. 

With  this  subject  one  calorimeter  experiment  was  made,  in  which  the  sub- 
ject fasted  and  the  bed  calorimeter  was  used;  three  respiration  experiments 
were  also  made,  each  of  which  was  preceded  by  the  ingestion  of  food.  The 
vital  statistics  were  as  follovv^s: 

Date  of  birth,  March  16,  1863;  height,  181  cm.;  range  in  body-weight 
without  clothing  during  experiments,  55.3  to  58.2  kilos. 
Respiration  Experiment  No.  R1. 

Date,  August  1,  1910.     Body-weight  without  clothing,  56.4  kilos. 

This  was  intended  to  be  only  a  trial  experiment,  since  it  was  the  first 
respiration  experiment  with  this  subject.  After  a  breakfast  consisting  of  36 
gms.  of  Quaker  oats  (weight  uncooked),  125  c.c.  of  cream,  2  eggs,  one-half 
biscuit,  and  2  cupfuls  of  coffee  containing  100  c.c.  of  sugarless  diluted  milk, 
also  4  grams  of  sodium  bicarbonate  in  water,  the  subject  came  to  the  labora- 
tory and  lay  down  upon  the  couch  at  9^  50™  a.  m.  The  experiment  included 
but  one  period  of  12  minutes,  beginning  at  9''  55"  a.  m.  and  ending  at  lO''  07°* 
a.  m.  The  pulse-rate  ranged  from  95  to  100,  and  the  respiration-rate  from 
15  to  17.     The  results  of  the  experiment  are  given  in  table  66. 


STATISTICS   OF   EXPERIMENTS. 


57 


58 


METABOLISM    IN    SEVERE    DIABETES. 


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STATISTICS   OF   EXPERIMENTS. 


59 


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60 


METABOLISM   IN    SEVERE   DIABETES. 


Respiration  Experiment  No.  R2. 

Date,  August  15,  1910.     Body-weight  without  clothing,  58.2  kilos. 

This  experiment  was  preceded  by  the  ingestion  of  food,  and  consisted  of 
but  one  14-minute  period,  beginning  at  lO''  15""  a.  m.  The  results  of  the  experi- 
ment are  given  in  table  66. 

Table  66. — Results  of  respiration  experiments  Nos.  Rl  to  RS^ 


Experi- 
ment 
No. 

Rl 

R2 
R3 

Date  and  time. 

j     Carbon         Oxveen 
Duration.  !    ,Sted   „^bsorbed 
per  minute.   Pe-"  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

1910. 
Aug.    1.     9''55"a.m 

Aug.  15.  lO'-lS^a.m 

Sept.  15.    l''07™p.m 

1    25    p.m 

Average 

min.  sec.            ex. 
12      6             »227 

c.c. 
2310 

0.73 

98 

16 

14    24             8  224 

'334 

0.67 

81 

15 

11    52 
11    58 

207 
208 

310 
310 

.67 
.67 

82 
83 

16 
18 

i       *208               «310 

1 

.67                83 

17 

1  Food  v.-as  taken  by  the  subject  before  each  of  these  experiments. 

^Carbon  dioxide  eUminated  per  kilogram  per  minute,  4.02  c.c;  oxygen  absorbed  per  kilogram  per  minute,  5.50  c.c. 

Tho  urine  collected  between  7''  So'"  and  10°  25"  a.m.  amounted  to  340  c.c.  and  contained  2.47  gms.  nitrogen  and 

10.5  gms.  sugar. 
'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.85  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  5.74  c.c. 
*  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.64  c.c;  oxygen  absorbed  per  kilogram  per  minute,  5.42  c.c. 

Respiration  Experiment  No.  R3. 

Date,  September  15,  1910.     Body-weight  without  clothing,  57.2  kilos. 

This  experiment  was  also  made  after  the  ingestion  of  food  and  included 
two  periods,  each  of  12  minutes.  The  subject  arrived  at  the  laboratory  at 
12''  45"'  p.  m.,  and  lay  on  the  couch  for  about  10  minutes  before  the  experiment 
began  at  l'>  07™  p.  m.  The  stethoscope  was  not  used,  the  pulse-rate  being 
counted  at  the  wrist.  The  subject  lay  perfectly  quiet  throughout  the  whole 
experiment.     The  results  are  given  in  tables  66  and  67. 

Table  67. — Statistics  of  iirine — Respiration  experiment  No.  R  3. 


D:ite  and  period. 

Sept.  15,  1910:1 

7''  30"»  a.m.  to  lo''  00"'  a.m 

10    00    a.m.         1    00    p.m     ... 

Volume. 

Total          t;  „„, 
nitrogen.       "^"S^"^" 

c.c. 

250 

433 

145 

1115 

1310 

gms.           gms. 
1.65              9.9 
1.99            19.2 
.65              6.6 
4.01            43.6 

4.68            44.4 

1    00    p.m.         1    55    p.m 

1    55    p.m.         9    30    p.m 

Sept.  15-16,  1910: 

9>' 30^"  p.m.  to   7'>30'"a.m 

'  Subject  probably  ate  food  as  usual. 

Calorimeter  Experiment  No.  R4. 

Date,  May  12,  1911.     Body-weight  without  clothing,  55.3  kilos. 

The  subject  fasted  in  this  experiment,  coming  to  the  laboratory  at  7''  20°* 
a.  m.,  without  breakfast.  This  was  the  first  time  the  bed  calorimeter  had  been 
used  with  this  subject  and,  after  he  entered  the  apparatus  at  7*"  51™  a.  m.,  he 
seemed  somewhat  nervous  and  apprehensive,  asked  a  great  many  questions, 
and  moved  around  considerably.  The  experiment  began  at  8^  54™  a.  m.,  and 
continued  for  two  periods,  one  of  45  minutes  and  the  other  of  47  minutes,  end- 
ing at  10''  26™  a.  m.  Especially  during  the  first  period  he  was  more  active  than 
the  average  subject,  telephoning,  urinating,  and  drinking  water.  The  pulse-rate 
was  obtained  as  usual  Avith  the  stethoscope,  and  the  two  pneumographs  were 


STATISTICS   OF   EXPERIMENTS. 


61 


used  to  obtain  records  of  the  respiration  rate  and  the  major  movements.  At 
9''  20"'  a.  m.  the  subject  drank  60  c.c.  of  water.  After  coming  to  the  laboratory 
in  the  morning  he  urinated  at  7^  28""  a.  m.,  also  during  the  experiment,  at 
9*^  15""  a.  m.,  and  after  the  experiment  was  over,  at  10^  40""  a.  m.  The  records 
are  given  in  tables  68  and  69. 

Table  68. — Measurements  of  metabolism — Calorimeter  experiment  No.  R4- 


Date  and  period. 

"^el'mmaief^         Oxy. en  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

mfnu'te.       Total. 

Per 
minute. 

May  12,  1911: 

8'' 54™  a.m.  to   gi'Sg^a.m 

9    39    a.m.       10    26    a.m 

gms. 
17.1 
17.9 

c.c.           gms. 

193  18.2 

194  ,      17.4 

c.c. 
283 
260 

0.68 
.75 

70 
70 

17 
16 

Total  1  hr.  32min.' 

35.0 

194      1      35.6 

271      j        .72      1        70 

17 

1  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.51  c.c  :  oxygen  absorbed  per  kilogram  per  minute,  4.90  c.c. 

Table  69. — Statistics  of  urine — Calorimeter  experiment  No.  R4- 


1 
1 

Date  and  period.                    Volume. 

Specific 
gravity. 

Total 
nitrogen. 

Sugar. 

May  12,  1911:                                                c.c. 
7^  28™  a.m 115 

1.026 
1.025 
1.024 

gms. 
0.55 
1.19 

.87 

gms. 
2.8 
5.9 
3.9 

7    28    a.m.  to    g^^  15™  a.m 251 

9    15    a.m.       10    40    a.m 182 

CASE  S. 
DESCRIPTION    OF   THE    CASE. 

Male;  born  1853;  married;  merchant;  onset  of  diabetes  in  1899;  came 
under  our  observation  May  12,  1910;  died  in  coma  October  19,  1910. 

Family  history. — No  history  of  diabetes  mellitus.  Father  died  at  87; 
mother  of  cancer;  one  brother  of  liver  trouble;  one  brother  and  one  sister  in 
infanc}^;  one  son  33  years  old,  well. 

Past  history. — Health  neither  very  poor  nor  very  good.  Measles,  mumps, 
herpes,  hemorrhoids. 

General  history  of  case. — The  diabetes  was  first  apparent  in  1899  with 
m.alaise.  The  greatest  quantity  of  sugar  noted  was  3.5  per  cent,  while  the 
greatest  volum.e  of  urine  was  2400  c.c.  The  general  condition  of  the  patient 
was  excellent.  The  patient  was  under  observation  for  only  a  short  period  of 
time.  Death  occurred  some  5  months  afterwards  while  the  patient  was  travel- 
ing, and  was  considered  due  to  coma. 

Physical  examination. — Greatest  weight,  April  1901,  was  71.1  kilos,  with- 
out clothes;  May  13,  1910,  57.6  kilos,  undressed.  Height,  177  cm.;  tour  de 
taille  76  cm.;  pupils  equal,  reacted;  knee-jerk  normal;  blood-pressure  120; 
pulse  72.  Nothing  abnormal  noted  about  the  heart  and  lungs.  Liver  extended 
2  fingers'  breadth  below  costal  margin.  Spleen  extended  to  the  costal  margin 
and  was  hard. 

Urine  data. — The  urinary  records  of  the  case  are  given  in  table  70. 
Throughout  the  observation  of  the  urine  the  reaction  in  all  cases  was  acid,  and 
the  slightest  possible  trace  of  albumen  was  present  on  every  day  except  May 
16-17.  On  all  days  of  the  observation,  8  grams  of  sodium  bicarbonate  were 
given. 


62 


METABOLISM  IN    SEVERE   DIABETES. 


EXPERIMENTS   WITH    CASE    S. 

Two  experiments  were  made  with  this  subject,  in  both  of  which  the  respi- 
ration apparatus  was  used.  One  was  a  fasting  experiment  and  the  other 
followed  the  ingestion  of  oatmeal.     The  vital  statistics  were  as  follows: 

Date  of  birth, ,  1853;  height,  177  cm.;  bodj^-weight  without  clothing 

during  experiments,  58  kilos. 

Table  70. — Clinical  chart — Case  S. 


Date. 

i 

a 

"3 
<& 
S 

_3 

o 
OQ 

1 

o 

"8 

s 

1 

Ammonia. 

Sugar. 

.S 
1 

i 
1  • 

O 

It 

•go 

is" 

■T3  O 
O 

1 

r  o 

§ 
1 

> 

5 

"Z 

H 

^fr> 

«'' 

« 

O 

O 

n 

1910. 

C.C. 

gms. 

gms. 

p.ct. 

gms. 

gms. 

gms. 

gms. 

kilos. 

May  12-13 

1023 

0 

21.4 

57.6 

13-14 

1920 

1019 

S1.+ 

13.1 

1.5 

9 

4 

ie 

8 

3  20 

+  5 

57.8 

14-15 

2520 

1020 

++ 

13.8 

... 

34 

10 

20 

-15 

57.7 

15-16 

2400 

1020 

+ 

11.7 

39 

19 

15 

-25 

57.6 

16-17 

1830 

1022 

S1.+ 

10.6 

38 

22 

20 

-20 

57.7 

17-18 

1920 

1022 

+ 

10.4 

1.6 

12 

7 

34 

19 

20 

-15 

58  2 

18-19 

1860 

1019 

++ 

7  3 

1.2 

13 

S 

26 

15 

45 

+20 

57.9 

19-20 

1800 

,     1021 

+ 

29 

45 

58.1 

20-21 

2220 

1024 

0 

11.5 

58 

44 

45 

-is 

58.3 

21-22 

1800 

1    1021 

++ 

8.6 

31 

18 

45 

+15 

57.9 

22-23 

1740 

j     1023 

+ 

9.5 

36 

24 

45 

+10 

57.5 

18  gms.  sodium  bicarbonate  given  eacli  day.    Beginning  May  13  the  diet  contained  200+  gms.  fat  and  12  gms. 
alcohol.  2 Per  cent.  3i2±  gms.  nitrogen. 

Respiration  Experiment  No.  Si. 

Date,  May  18,  1910.     Body-weight  without  clothing,  58  kilos. 

As  this  subject  had  not  previously  been  experimented  upon  and  was 
somewhat  elderlj^,  only  three  periods  of  10  to  11  minutes  were  run,  so  as  not  to 
overtire  him.  The  subject  came  from  the  hospital  at  8''  15'"  a.  m.,  without 
breakfast,  and  lay  down  upon  the  couch  for  some  10  minutes  before  the  experi- 
ment began  at  S^  40™  a.  m.  Surgeon's  plaster  could  not  be  used  on  account  of 
his  moustache  and  beard.  The  stethoscope,  also  the  pneumographs  about  the 
chest  and  thighs,  were  used.  The  experiment  was  without  incident,  the  sub- 
ject lying  quietly  throughout.  After  the  experiment  was  over  the  subject 
urinated  at  9''  45™  a.  m.     The  results  are  given  in  table  71. 

Table  71. — Results  of  respiration  experiment  No.  SI. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

May  18,  1910: 

8'>40"a.m 

9    03    a.m 

9    25    a.m 

min.   sec. 
11     21 
10    20 
10      9 

c.c. 
148 
1.54 
156 

c.c. 

2i8 
208 

6!7i 

75 

59 
58 
67 

8 
9 
9 

U53 

1213        i            7S 

58 

9 

>Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.64  c.c;  oxygen  absorbed  per  kilogram  per 
minute,  3.67  c.c.  The  urine  collected  between  8  and  9*^  40™  a.m.  amounted  to  92  c.c.  and 
contained  0.53  gm.  nitrogen  and  1.9  gms.  sugar. 


STATISTICS    OF   EXPERIMENTS. 


63 


Respiration  Experiment  No.  S2. 

Date,  May  21,  1910.     Body-weight  without  clothing,  58  kilos. 

The  subject  came  to  the  laboratory  after  eating  at  the  hospital  a  break- 
fast of  approximately  250  gms.  of  cooked  oatmeal  between  7''  30™  a.  m.  and 
7''  45™  a.  m.  He  lay  down  upon  the  couch  at  8^  10™  a.  m.,  and  the  experiment 
began  at  8''  16™  a.  m.,  continuing  for  four  periods,  11  to  12  minutes  long,  with 
intermissions  of  12  to  15  minutes.  Both  pneumographs  were  used.  The 
subject  urinated  at  7''  45™  a.  m.,  before  the  experiment,  and  again  after  the 
experiment,  at  10  a.  m.     The  data  are  given  in  table  72. 

Table  72. — Results  of  respiration  experiment  No.  S2. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

May  21,  1910: 

'S'l  le^a.m 

8  43    a.m 

9  10    a.m 

9    34    a.m 

min.  sec. 

11  14 

12  5 

11  41 

12  21 

c.c. 
162 
162 
156 
162 

c.c. 

208 
223 
212 
213 

0.78 
.72 
.73 

.76 

62 
58 
58 
57 

8 
9 
9 
10 

2  161 

2214 

75      !        ."ia 

9 

•  Subject  ate  oatmeal  for  breakfast  between  7*'  30""  and  7''  45™  a.m. 

2  Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.78  c.c;  oxygen  absorbed  per  kilogram  per  minute,  3.69 c.c. 

The  urine  collected  between  7^  45™  and  10  a.m.  amounted  to  245  c.c.  and  contained  1.04  gms.  nitrogen  and 

10.2  gms.  sugar. 

In  order  to  compare  his  metabolism  with  that  of  a  normal  subject  after 
eating  oatmeal,  an  experiment  was  made  with  another  subject  who  had  eaten 
434  gms.  of  cooked  oatmeal.  The  time  intervening  between  the  ingestion  of 
the  oatmeal  and  the  beginning  of  the  experiment  was  the  same  as  in  the  experi- 
ment with  the  diabetic.  The  respiratory  quotients  obtained  with  the  normal 
subject  were  0.806,  0.807,  0.854,  and  0.780,  respectively. 

CASE  T. 

DESCRIPTION    OF   THE    CASE. 

Male;  born  1867;  married;  farmer;  onset  of  diabetes  in  September  1908; 
diagnosed  November  1908;  came  under  our  observation  December  5,  1910; 
died  in  coma  March  5,  1911. 

Family  history. — No  history  of  diabetes  mellitus.  Father  died  at  77 
years  of  heart  disease;  mother  at  63  years  of  cancer;  wife  and  six  children  well; 
one  child  died  of  heart  disease. 

Past  history.— Measles,  mumps,  whooping-cough,  scarlet  fever. 

General  history  of  case. — September  1908,  there  were  polydipsia  and  poly- 
uria, with  loss  of  weight  for  a  month  previous  to  the  diagnosis  in  November 
1908.  The  chief  symptom  was  weakness.  Carbuncles  and  boils  developed 
in  October  1910,  and  the  patient  also  suffered  from  constipation.  The  diet 
was  at  no  time  strict,  as  the  feebleness  of  the  patient,  his  inability  to  bear 
sodium  bicarbonate  well,  and  the  severity  of  the  acidosis  made  restrictions  of 
diet  appear  impracticable.  The  patient  failed  to  respond  to  diet,  and  died  in 
coma  March  5,  1911,  shortly  after  returning  home. 

Physical  examination. — Greatest  weight  without  clothing,  71.2  kilos.; 
normal  weight  without  clothing,  67.0  kilos.;  weight  December  5,  1910,  52.7 
kilos,  without  clothing.  Height,  180  cm.  Pupils  equal  and  reacted.  Knee- 
jerk  normal.  No  edema.  Lungs  and  heart  normal.  Pulse-rate,  72.  There 
were  numerous  boils  and  ulcers,  some  of  which  were  partially  healed,  over  the 
clavicle,  neck,  arms,  and  back — a  truly  pitiable  sight.  The  breath  had  an 
acetone  odor. 


64 


METABOLISM   IN   SEVERE   DIABETES. 


Urine  data. — The  greatest  quantity  of  urine  was  10,000  c.c.  at  about  the 
time  of  onset.  When  the  patient  came  under  observation  the  acidosis  was 
extreme;  this  is  indicated  by  the  6  grams  of  ammonia  shown  in  table  73,  which 
gives  the  urinary  record  during  observation.  The  reaction  of  the  urine  during 
this  period  was  acid  throughout,  with  a  shght  trace  of  albumen.  The  carbo- 
hydrate balance  was  for  the  most  part  minus  throughout.  Beginning  January 
31,  1911,  22  grams  of  alcohol  were  given  daily. 


Table  73 

— Clinical  char 

—Ca 

seT. 

Date. 

i 

•c 

3 

o 

s 

"3 

> 

i 

1 
o 

'■§ 

5 

3 
>> 

■| 

1 

j  Ammonia. 

! 

Sugar. 

i 

O 

6 

•3 

I 
<a   . 

-5S 

M  S3 
O 
X) 

4 
O 

o 

J: 

"53  o 
^" 

pa 

"3 
1 

P 

11 

.2  fed 

1910. 
Dec.    4-5 

c.c. 

5000 
3  5000 

6000 
•3200 
4500  ± 
3400 
4700 
4480 
5100 
5740 
5700 
2980 
2960 
4000 
3420 
5000 
4000 
4380 
4580 
4180 
3305 
3335 
3190 
3120 

1037 
1033 

1037 
1035 
1037 
1036 
1031 
1029 
1030 

i627 
1032 
1037 
1033 
1032 
1030 
1033 
1033 
1032 
1031 
1032 
1027 
1023 
1028 

0 

Sl.-I- 

S1.+ 

■■++ 

++ 

+++ 

+++ 

+++ 

+++ 

++ 

++ 

++ 

++ 

+ 

+ 

++ 

++ 

+++ 

+ 

++ 

++ 

+ 

+++ 

gms. 





43!3 
40.6 
50.1 
39.7 

30.2 

gms 

ie! 

18. 
17. 
13. 
11 
11. 
9. 
11. 

.    gms. 

p.ct. 

gms. 

+ 
+ 

+ 

i46 

230 
184 
219 
198 
179 
138 
73 
58 
128 

gms. 

"■1.2 
240 

408 
211 
279 
204 
197 
179 
204 
184 
171 
131 
178 
176 
150 
200 
168 
210 
174 
167 
119 
53 
57 
125 

gms. 

m 

200 
200 
200 
185 
165 
155 
140 
185 
150 
140 
140 
140 
140 
140 
140 
130 
15 
166 
115 

gms. 

:1 

+    5 
+  20 

-  20 

-  20 

-  15 

-  5 
+    5 

-  25 

-  10 

-  90 

-  45 

-  80 

-  60 

-  40 

-  10 

-  60 
-1-110 

-  15 

gms. 

■■ 

24 
30 
30 
30 
30 
20 
12 
12 
12 
12 
12 
12 
12 
12 
12 
12 
12 
12 

kilos. 

53.9 
52.7 
52.4 
50.9 
50.0 
51.7 
53.2 
53.1 
51.8 
50.6 
52.3 
52  7 
52.8 
62.8 
52.4 
53.2 
53.2 
52.6 
51.5 
51.5 
50.9 
52.2 

Dec.  28-29 

1911. 
Jan.   27-28 

Jan.   28-29 

Jan.   29-30 

Jan.   30-31 

Jan.31-Feb.  1 

Feb.    1-2 

Feb.    2-3 

Feb.    3-4 

Feb.    4-5      

Feb.    5-6 

Feb.    6-7 

Feb.    7-8 

...  1  .... 

Feb.    8-9 

6!6 

2 

I     ... 

3       ... 
3       5.5 
B       5.2 
7  i    5.5 
i       4.6 
[)       ... 

33.3 
36.9 
38.7 
40.7 

Feb.    9-10 

Feb.  10-11 

Feb.  11-12 

Feb.  12-13 

Feb.  13-14 

Feb.  14-15 

Feb.  15-16* 

Feb.  16-17« 

Feb.  17-18 

'Whisky,  45  gms.  daily  throughout  stay  in  hospital.  'Per  cent. 

'  Urinary  sediment  contained  many  fine  and  coarse  granular  casts. 

<  18  hours.     Urinary  sediment  contained  many  hyaline,  fine,  and  coarse  granular  casta. 

'Vegetable  daj'  240  c.c.  cream,  4  eggs.        'Oatmeal  da5%  240  gms.  oatmeal,  240  gms.  butter,  240  c.c.  cream. 

EXPERIMENTS   WITH    CASE   T, 

Two  fasting  experiments  were  made  with  this  subject,  in  both  of  which  the 
bed  calorimeter  was  used.  A  comparison  of  the  data  obtained  is  made  in  table 
76.     The  vital  statistics  were  as  follows: 

Date  of  birth,  1867;  height,  180  cm.;  range  in  body-weight  without  cloth- 
ing during  experiments,  51.3  to  51.5  kilos. 

Calorimeter  Experiment  No.  T1. 

Date,  February  14,  1911.     Body-weight  without  clothing,  51.5  kilos. 

Previous  to  this  experiment  no  food  had  been  taken  by  the  subject  since 
the  evening  meal  of  the  day  before,  with  the  exception  of  a  cupful  of  coffee  at 
Q^  30"  a.  m.  When  the  subject  arrived  at  the  laboratory  at  8  a.  m.  he  appeared 
to  be  a  very  weak,  sick  man,  and  somewhat  apprehensive  in  regard  to  the 
experiment.  He  was  dressed  in  unusually  warm,  heavy  clothing,  and  on  enter- 
ing the  bed  calorimeter,  at  8*^  26""  a.  m.,  was  also  covered  with  a  blanket.  The 
experiment  began  at  9^  18™  a.  m.  and  continued  for  two  45-minute  periods, 
ending  at  lO""  48™  a.  m.  During  the  whole  experiment  the  subject  lay  very 
quietly  on  his  back,  without  reading,  save  near  the  close  of  the  first  period, 


STATISTICS    OF   EXPERIMENTS. 


65 


when  he  moved  considerably.  After  the  experiment  was  over  he  seemed  to  be 
very  tired  and  glad  that  it  was  over.  Before  coming  to  the  laboratory  the  sub- 
ject urinated  at  7''  30™  a.  m.,  and  again,  after  the  experiment,  at  U''  03""  a.  m. 
The  records  of  the  experiment  are  given  in  table  74. 

Table  74. — Measurements  of  metabolism — Calorimeter  experiment  No.  Tl. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

I    Total.       J-,^ 

Total.    1      f^\ 
j  mmute. 

Feb.  14,  1911: 

iQl"  18™  a.m.  to  lO''  03"  a.m.  . . . 
10    03    a.m.       10    48    a.m.... 

Total  1  hr.  30  min.2 

1     gms.             c.c. 
..       15.0      j        170 
..       15.2      !        172 

gms.             c.c. 
15.0              233 
15.8              246 

0.73 
.70 

66 
68 

15 
16 

. .;      30.2              171 

30.8      [        240 

•• 

'  Subject  drank  a  cup  of  coffee  at  6"^  30™  a.m. 

-Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.32  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.66  c.c. 

The  urine  collected  between  7°  30™  a.m.  and  11°  03™  a.m.  amounted  to  345  c.c,  specific  gravity  1.030,  and 

contained  1.52  gms.  nitrogen  and  12.4  gms.  sugar. 

CALORIMETER   EXPERIMENT   No.    T2. 

Date,  February  16,  1911.     Bodj-weight  without  clothing,  51.3  kilos. 

This  was  also  a  fasting  experiment,  neither  food  nor  coffee  being  taken 
after  the  evening  meal  of  the  day  before.  The  subject  came  to  the  laboratory 
at  7*^  30™  a.  m.,  and  the  experiment  began  at  8''  47™  a.  m.  After  two  45- 
minute  periods  the  experiment  ended  at  lO''  17™  a.  m.  Throughout  the  whole 
experiment  the  subject  lay  quietly  on  his  back.  He  appeared  to  be  somewhat 
tired  at  the  end  of  the  experimental  period,  but  had  evidently  become  more 

Table  75. — Measurements  of  metabolism — Calorimeter  experiment  No.  T2. 


Date  and  period. 


Carbon  dioxide 
eliminated. 


Total. 


Per 
minute. 


Oxygen  absorbed. 


Total. 


Per 
minute. 


Respi-      Average  i  Average 

ratory         pulse-     I  respira- 

quotient.  [     rate.      !  tion  rate. 


Feb.  16.  1911: 

g*"  47™  a.m.  to   9'' 32™  a.m. 
9    32    a.m.       10    17    a.m. 

Total!  hr.  30  min.i 


gms. 
14.8 
14.7 


c.c. 

168 
167 


gms. 
14.0 
14.7 


c.c. 
217 
229 


0.77 
.73 


29.5 


167 


28.7 


223 


•Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.26  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.35  c.c. 
The  urine  collected  between  7  and  711  42™  a.m.  amounted  to  80  c.c,  specific  gravity,  1.030,  and  contained  0.. 34 
gms.  nitrogen  and  2.4  gm^.  sugar. 

accustomed  to  the  apparatus  and  the  routine.  The  pulse  and  respiration 
rates  were  obtained  in  the  usual  way  with  the  stethoscope  and  pneumograph,  a 
second  pneumograph  being  used  about  the  thighs  to  give  a  record  of  any  major 
movements.  The  subject  urinated  at  7^  42™  a.  m.,  but  was  unable  to  urinate 
again  after  the  experiment  was  over.  The  records  of  the  experiment  are  given 
in  table  75. 

Table  76. — Comparison  of  metabolism  experiments  in  the  bed  calorimeter  vnth  Case  T 
in  experiments  without  food. 


Experi-                         Weight 
ment         Date.              of 
No.    j                        subject. 

Length 
of  ex- 
periment. 

Per  minute. 

r^aSl^S^--P^^ 
<l-tien\|^"^;^.l*-„'f,^ 

Carbon 

dioxide 

eliminated. 

Oxygen 
absorbed. 

1911.             Ulos. 
Tl      Feb.  141..       51.5 
T2      Feb.  16....       51.3 

hrs.  min. 
1      30 
1      30 

c.c. 
171 

167 

c.c. 
240 
223 

0.71             66             15.5 
.75             68       i      15.0 

'  2  hours  and  48  minutes  before  the  experiment  began  the  subject  drank  a  cup  of  coffee. 


66  METABOLISM   IN   SEVERE   DIABETES. 

CASE  U. 
DESCRIPTION    OF   THE    CASE. 

Female;  born  November  16,  1873;  single;  teacher;  onset  of  diabetes,  April 
1909;  sugar  found  in  the  urine  August  1,  1909;  first  came  under  our  observa- 
tion April  18,  1910;  died  in  coma  August  11,  1911. 

Family  history. — No  history  of  diabetes  in  family.  Father,  mother,  and 
two  brothers  well;  one  brother  has  arthritis  deformans. 

Past  history. — Healthy ;  scarlet  fever  three  times,  measles,  mumps,  whoop- 
ing cough.  Pneumonia  at  14.  Catamenia  normal.  Overwork  and  worry, 
especially  because  of  the  brother's  illness. 

General  history  of  case. — In  April  1909  there  were  loss  of  weight  and  poly- 
dipsia. In  May  1909,  polyuria,  furuncles,  and  weariness  appeared.  Follow- 
ing the  discovery  of  sugar  in  the  urine,  thirst  and  nervousness  nearly  disap- 
peared and  the  strength  improved;  nevertheless  the  patient  had  polyphagia. 
The  course  of  the  disease  is  shown  in  table  77.  Notwithstanding  the  severity 
of  the  disease,  the  patient  taught  daily  until  May  1911.  There  was  a  gradual 
loss  in  strength,  as  well  as  in  weight,  and  she  died  in  coma  August  11, 1911. 

Physical  examination. — Greatest  weight,  summer  of  1908,  53.1  kilos.; 
April  1909, 49.9  kilos. ;  May  1909,  45.4  kilos. ;  August  1909,  41.7  kilos. ;  April  18, 
1910,  39.7  kilos.  Height,  160  cm.  Pupils  equal  and  reacted  to  light.  Knee- 
jerks  normal.  Bilateral  submaxillar}^  glands.  Emaciated.  Tongue  and  teeth 
normal.  Heart  just  within  mammillary  line,  systolic  at  the  apex.  Pulse- 
rate,  112.  Blood-pressure,  100.  Lungs  normal.  Abdomen,  right  movable 
kidney  but  otherwise  normal.     No  edema  of  lower  extremities. 

Urine  data. — The  quantity  of  urine  August  1,  1909,  was  5,750  c.c;  spe- 
cific gravity  1.040.  The  reaction  of  the  urine  was  acid  throughout  the  period  of 
observation.  The  acidosis  was  marked  from  the  very  first,  but  decreased  sub- 
sequently with  the  use  of  sodium  bicarbonate.  The  greatest  quantity  of 
ammonia  was  5.2  grams,  April  22, 1911.  On  March  11,  1911,  the  urinary  sedi- 
ment contained  numerous  fine  and  coarse  granular  casts.  The  quantity  of 
sugar  in  the  urine  when  the  patient  first  came  under  observation  amounted  to 
7.2  per  cent  in  a  single  specimen,  and  to  6.2  per  cent  (132  grams)  during  the  24 
hours  of  April  19-20,  1911.  This  steadily  decreased,  but  the  patient  never 
became  sugar-free.     Albumen  never  exceeded  a  slight  trace. 

EXPERIMENTS   WITH    CASE   U. 

With  this  subject  three  bed  calorimeter  experiments  were  made  and  nine 
respiration  experiments.  A  number  of  these  were  made  in  series.  Series  I 
included  a  calorimeter  experiment  (U5)  in  which  the  subject  fasted,  and  a 
respiration  experiment  (U6).  In  this  latter  experiment  the  subject  fasted  the 
first  two  periods,  then  took  food.  Series  II,  which  included  five  experiments, 
began  with  a  respiration  experiment  (U8),  which  was  followed  by  an  oatmeal 
breakfast ;  an  experiment  was  then  made  with  the  bed  calorimeter  (U  9) ,  which 
was  in  turn  succeeded  by  a  second  respiration  experiment  (UIO).  The  sub- 
ject spent  the  night  in  the  bed  calorimeter,  metabolism  measurements  being 
made  during  the  latter  part  of  the  night  (UU).  In  the  morning  of  the  next 
day,  a  third  respiration  experiment  (U 12)  was  made  after  a  beefsteak  break- 
fast, completing  the  series.  A  comparison  of  the  data  obtained  in  the  calo- 
rimeter experiments  is  given  in  table  92.  The  vital  statistics  for  this  subject 
are  as  follows: 


STATISTICS    OF   EXPERIMENTS. 


67 


Date  of  birth,  November  16,  1873;  height,  160  cm.;  range  of  body-weight 
without  clothing  during  experiments,  35.8  to  44.2  kilos. 

Table  77. — Clinical  chart — Case  U. 


Date. 


1910. 
Apr.  17-lS., 
Apr.  19-20., 
Apr.  22-23. 
Apr.  2.5-26. 
Apr.  29-30. 
May  1-2. 
May  4-5. 
May  9-10. 
May  13-14. 
May  18-19  5 
May  19-20. 
May  23-24. 
May  25-26. 
May  26-27' 
June  27-28. 
July  8-  9. 
"  ■      14-15. 

25-26. 
1-  2. 

17-18. 


July 
July 
Aug. 

Aug. 


Sept.  12-13. 
Oct.  7-  8. 
Nov.  4-  5. 
Nov.  22-23. 
Dec.  10-17. 

1911. 
Jan.  13-14. 
Feb.  10-11. 
Mar.  10-11. 
Mar.  24-25. 
Mar.  311 


I/--- 

1-  2. 

2-  3. 
21-22. 
19-20. 


Apr. 

Apr. 
Apr. 
Apr. 
May 
May  311 
June  1 / ■ ■ 
June  1-2". 
June  2-3  '2. 
July  6-7.. 


c.c. 

2Uo 

2000 

1875 

2000 

2000 

2375 

1  2190 

1  2500 

I  2125 

!  6  325 

!  2250 

i  2000 

275 

2500 

2666 

2375 

I  2500 
2000 
27.50 
27.50 
2750 

i  2750 
3250 

I' 3000 
3250 

I  2420 

li«2330 
3135 

3000 
I  3250 


1805 

3500 


1039 
1042 
1032 
1030 
1031 
1030 
1033 
1023 
1026 
1027 

1634 


1C35 
1035 
1034 
1032 
1026 
1030 
1029 
1030 
1028 
1033 
1031 

1031 
1025 
1024 
1030 


1029 
1029 

1032 


1021 

1027 


0 

V.sl.-h 

V.S1.+ 

0 

++ 

+ 
+ 

+ 

-1- 

+ 
■■++ 


"++ 

+++ 

+++ 

++++ 

++++ 

++++ 
+++ 
+++ 


+++ 
+++ 


++ 


11.5 
9.0 
1.2 

10.7 
9.8 
0.6 

25.5 


13.8 


13.3 
10.0 


13.3 


12.5 

9.5 

9.2 
9.9 

13.6 


6.9 


Ammonia. 


4.4 
4.3 


1.7 


2.8 

i'.i 

4.0 
4.4 
4.7 
5.0 

3  6 

3.7 
4.0 

5.2 

4.7 


p.ct. 


31.5 
39.3 


26.9 


Sugar. 


gms.  I  gms. 
+  '7.2 
+  132 
68 
79 
60 
56 
67 
31 
60 
51 


27.0 
32!9 


31.2  1  120 


74 
15 

104 
77 
3 

6135 


50 


72 


117 
90 
156 


33.1 
33.2 

31.4 


75 
97 

105 
127 

'4.74 


36 

158 


86 


120 


90 
52 

77 
105 


91 
66 
137 


Diet.i 


126 


70 
80 
70 
80 
63 
75 
100 

'76 
95 


-10 
+20 
+15 
+15 
+35 
+15 
+25 

-35 

+20 


+10 

+25 

-25 
+15 
+  5 
-30 
-20 

-25 
-40 
-25 
-80 


-40 
-70 


>?3 


kilos. 


39.5 
40.2 
40.4 
39.5 
39.0 
38.3 
39.3 

46!5 


42.3 


43.3 
41.8 
43.6 
44.0 
43.6 
41.1 
41.1 
40.9 

40.4 
38.2 
37.2 
39.5 


37.7 
37.0 


-85       12     36.1 


1  Fat  in  diet,  May  9-10, 175  gms.;  Dec.  16-17, 150±  gms. 

'Approximate. 

'Per  cent. 

«16  gms.  NaHCOa  given  daily.  May  14,  15,  and  16. 

'  120  gms.  oatmeal,  120  gms.  butter,  240  c.c.  cream, 

240  c.c.  milk,  4  eggs. 
'From  S*"  30™  to  U*"  50™  a.m..  May  19. 


'  From  7  to  9*'  45"  a.m.,  May  26. 

*By  fermentation. 

'  Urinary  sediment  contained  fine  and  coarse  granular 

casts. 
i''23  hours  40  minutes. 
"  12  flours. 
'-23  flours  25  minutes. 


Respiration  Experiment  No.  Ul. 

Date,  May  14,  1910.     Body-weight  without  clothing,  39.0  kilos. 

This  experiment  was  made  simply  to  accustom  the  subject  to  the  respira- 
tion apparatus,  and  consisted  of  but  one  10-minute  period,  beginning  at  9''  55™ 
a.m.  The  breakfast  for  that  morning  was  an  egg  and  an  orange.  The  stetho- 
scope and  pneumograph  Avere  not  used,  and  no  records  of  pulse  and  respiration 
were  taken  other  than  two  records  of  the  respiration  from  the  tension  equalizer, 
which  gave  an  average  of  20  respirations  to  the  minute.  The  carbon  dioxide 
eliminated  per  minute  was  155  c.c,  and  per  kilogram  per  minute  3.97  c.c. 
The  oxygen  absorbed  per  minute  was  210  c.c,  and  per  kilogram  per  minute 
5.38  c.c.     The  respiratory  quotient  was  0.74. 


68 


METABOLISM   IN    SEVERE   DIABETES. 


Respiration  Experiment  No.  U2. 

Date,  May  19,  1910.     Body-weight  without  clothing,  39.3  kilos. 

A  breakfast  consisting  of  a  dish  of  oatmeal,  an  egg,  a  piece  of  bacon,  and  a 
cup  of  coffee  was  taken  before  the  experiment.  The  day  preceding  was  an 
"oatmeal  day,"  and  as  the  subject  usually  felt  considerably  better  on  these 
days,  it  seemed  desirable  to  determine  the  respiratory  quotient  under  such 
circumstances. 

The  subject  arrived  at  the  laboratoiy  about  10^  15""  a.m.,  lay  down  on  the 
couch  at  10^  30"  a.  m.,  and  the  experiment  began  at  10^  40""  a.  m.,  continu- 
ing for  three  periods  of  10  to  11  minutes,  with  intermissions  of  9  to  12  minutes. 
The  subject  urinated  before  the  experiment  at  8^  30™  a.  m.,  and  afterwards  at 
!!•»  SO""  a.  m.     The  records  of  the  experiment  may  be  found  in  table  78. 

Table  78. — Results  of  respiration  experiment  No.  U  2. 


Date  and  time. 

Carbon 

D-^tion.  ^,dio;^td 
1  per  minute. 

Oxygen 

absorbed 

per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

May  19, 1910: 

10*»40™a.m.i... 
11    01    a.m.... 
11    24    a.m.... 

Average 

min.   sec.            c.c. 
10    31                164 
10    37               157 
10    05               153 

c.c. 
222 
212 
217 

0.74 
.74 
.71 

90 
86 
87 

17 
17 
17 

=158        j        2217 

.73                 88 

17 

'The  subject  had  eaten  breakfast  as  usual. 

^Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.02  c.c:  oxygen  absorbed  per  kilogram  per 

minute,  5.52  c.c.    The  urine  collected  between  8°  30™  and  11^  50'°  a.m.  amounted  to  323  c.c. 

and  contained  1.20  gms.  nitrogen  and  15  gms.  sugar. 

Respiration  Experiment  No.  U3. 

Date,  May  26,  1910.     Body-weight  without  clothing,  41.2  kilos. 

The  subject  came  to  the  laboratorj^  without  breakfast  about  8^  30"*  a.  m., 
and  lay  down  upon  the  couch  for  10  minutes  before  the  experiment  began  at 
gh  44m  g^_  jjj  Three  periods  of  about  10  minutes  each  were  included  in  the 
experiment,  with  intermissions  of  10  to  12  minutes.  The  subject  urinated  at 
7  a.  m.  before  coming  to  the  laboratory,  and  again  at  9*"  45™  a.  m.  After  the 
experiment  was  over  she  was  given  a  breakfast  consisting  of  oatmeal  with 
cream,  and  boiled  eggs.     The  records  of  the  experiment  are  given  in  table  79. 

Table  79. —  Results  of  respiration  experiment  No.  US. 


Date  and  time. 

Carbon 

D-tion.   ^,fi°^ted 
1  per  minute. 

1 

Oxygen 
absorbed 
per  minute. 

i 

Respiratory!    Average 
quotient,      pulse-rate. 

Average 

respiration 

rate. 

May  26, 1910: 

8l'44'°a.m 

9    04    a.m 

9    26    a.m 

min.  sec.           c.c.                c.c. 
10    03      {         160                 215 
9    58                152                  182  (?) 
9    52                152                  214 

0.74                 85 
.84  (?)           89 
.71                 89 

17 
16 
16 

Average 

U55 

1204 

.76 

88 

16 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.76  c.c;  oxygen  absorbed  per  kilogram  per 
minute,  4.95  c.c.  The  urine  collected  between  7  and  9*'  45"  a.  m.  amounted  to  274  c.c.  and 
contained  0.64  gm.  nitrogen  and  2.8  gms.  sugar. 

Respiration  Experiment  No.  U4. 

Date,  September  13, 1910.     Body-weight  without  clothing,  44.2  kilos. 

This  experiment  followed  a  breakfast  taken  at  6^  45™  a.  m.  consisting  of 
oatmeal  and  cream,  small  amounts  of  melon  and  bacon,  and  an  egg.  She 
reached  the  laboratory  at  lO''  45™  a.  m.,  and  almost  immediately  lay  down 


STATISTICS    OF   EXPERIMENTS. 


69 


upon  the  couch.  The  experiment  began  at  11  a.  m.,  continued  for  three 
periods  of  12  to  13  minutes  each,  vnth  intermissions  of  12  to  16  minutes. 
Throughout  the  whole  experiment  the  subject  was  very  calm  and  quiet.  The 
results  of  the  experiment  are  given  in  table  80. 

Table  80. — Results  of  respiration  experiment  No.  U 4. 


{                           Carbon          j-. 
Date  and  time.      \  Duration.     „|f iPjnatld  '  absorbed 
;                                                          per  minute.  jP^^°^i''"t«- 

Respiratory 
quotient. 

Average    !    Average 
pulse-rate.    '^^"^^'^^ 

'  Sept.  13.  1910: 

ll''00™a.m.»... 
11    28    a.m.... 
11    53    a.m.... 

Average 

1 
min.   sec.   i         c.c. 

12  14                158 

13  12                154 
12    11                151 

c.c. 
224 
221 
212 

0.71 
.70 
.71 

90                   18 
88          i          18 
90          1          17 

2  154 

2  219 

.71 

89          j          18 

'  Subject  ate  breakfast  at  6*^  45™  a.m. 
2 Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.48  c.c;  oxygen  absorbed  per  kilogram  per 
minute,  4.95  c.c. 

Calorimeter  Experiment  No.  U5. 

Date,  March  31,  1911.     Body-weight  without  clothing,  39.9  kilos. 

This  was  the  initial  experiment  of  Series  I,  and  the  first  with  this  subject  in 
the  bed  calorimeter.  She  arrived  at  the  laboratory  at  7''  40™  a.  m.,  without 
breakfast,  and  entered  the  apparatus  at  T'^  55"  a.  m.  The  experiment  began 
at  8^  SO'"  a.  m.,  continuing  for  two  45-minute  periods,  ending  at  10^  20""  a.  m. 
The  subject  lay  very  quietly  reading  during  all  of  the  experiment,  except  near 
the  end  of  the  periods.  Both  pneumographs  and  the  stethoscope  were  used  to 
obtain  the  respiration-rate,  the  muscular  activity,  and  the  pulse-rate.  The 
results  of  the  experiment  are  given  in  tables  81  and  83. 

Table  81. — Measurements  of  metabolism — Calorimeter  experiment  No.  U5. 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total.          y^\ 
minute. 

Mar.  31,  1911: 

S^  50™  a.m.  to    9''  35™  a.m 

9    35     a.m.       10    20    a.m 

gms. 
13.6 
13.8 

c.c. 
154 
157 

84 

84 

18 
19 

Total  1  hr.  30  min.i 

27.4              155 

1 

1 

1  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.88  c.c. 

Respiration  Experiment  No.  U6. 

Date,  March  31,  1911,     Body-weight  without  clothing,  39.9  kilos. 

This  experiment,  which  was  the  second  and  last  of  Series  I,  was  divided 
into  two  parts,  the  subject  continuing  to  fast  after  leaving  the  bed  calorimeter 
until  after  the  first  two  periods  had  been  concluded.  She  then  took  100  grams 
levulose,  100  c.c.  weak  coffee,  and  175  c.c.  hot  water.  Six  additional  periods 
followed. 

The  experiment  began  at  10^  50"*  a.  m.,  the  two  fasting  periods  ending  at 
11^  SS^  a.  m.  The  food  was  taken  at  12  o'clock,  and  the  following  sLx  periods 
began  at  12^  16""  p.m.,  ending  at  3*"  08""  p.m.  Each  period  was  about  15  min- 
utes long,  the  intermissions  ranging  from  8  to  31  minutes.  The  subject  was 
awake  during  the  first  period,  and  coughed  once  at  10^  54"^  a.  m.,  also  several 
times  in  the  second  period.  There  were  slight  movements  reported  in  the  fourth, 
seventh,  and  eighth  periods.  The  subject  urinated  after  the  experiment  at 
3h  j5m  p  jjj     r^^Q  results  of  the  experiment  may  be  found  in  tables  82  and  83. 


70 


METABOLISM   IN    SEVERE   DIABETES. 


Table  82. — Results  of  respiration  experiment  No.  U6. 


1                      i     Carbon 
Date  and  time.            Duration.  :  e,[|Xa1fed 
I  per  minute. 

1                     1 

per  minute.     Quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

Mar.  31,  1911: 

Without  food — 
10b  50™  a.m.... 
11    23    a.m.... 

min.   sec.   ,         c.c. 

14  59      t          151 

15  0      1          145 

205        i       0.74 
211                  .69 

86 
88 

18 
17 

Average 

'        '148 

»208                  .71 

87 

17 

With  food— 

121^  16">p.m.2... 
12    44    p.m.... 

1  30    p.m.... 

2  05    p.m 

2    28    p.m 

2    53    p.m 

1 

15    10                172 
14    58                184 

14  47      j          180 

15  7                172 
14    27      '          171 
14    36      i          166 

271                  .63 
261                  .70 
246                 .73 
235                  .73 
250                  .68 
240                  .69 

90 
90 

87 
89 
89 

19 
19 
19 
18 
20 
19 

Average 

3 174 

»251                  .69 

89 

19 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  without  food,  3.71  c.c;  oxygon  absorbed  per  kilo- 
gram per  minute,  without  food,  5.21  c.c. 

-Subject  took  100  gms.  levulose  in  200  c.c.  of  very  weak  coffee  (hot)  at  12  noon. 

^Carbon  dioxide  eliminated  per  kilogram  per  minute,  with  food,  4.36  c.c;  oxygen  absorbed  per  kilo- 
gram per  minute,  with  food,  6.29  c.c. 

Table  83. — Statislics  of  wine — Calorimeter  experiynent  No.  U5  and 
respiration  experiment  No.  U  6. 


Date  and  period. 

Volume   !  ^P^"}^"      .'^°*^' 
volume.  ,  gravity,    nitrogen. 

Sugar. 

Mar.  31,  1911: 

7''  00™  a.m.  to  lO**  SO™  a.m 

10  30  a.m.  3  15  p.m.'.... 
Mar.  31-Apr.  1,  1911:  ^ 

S*"  15™  p.m.  to   7'»00™a.m 

c.c. 
246 
555 

1620 

1.029 
1.030 

gms. 
1.16 
1.50 

6.76 

gms. 

7.5 

24.5 

87.6 

'  Subject  took  100  gms.  levulose  in  200  c.c.  very  weak  hot  cofifee  at  12  noon. 


Respiration  Experiment  No.  U7. 

Date,  April  2, 1911.     Body-weight  without  clothing,  39.8  kilos. 

This  experiment  was  (like  U6)  divided  into  two  parts,  the  first  three 
periods  being  fasting  periods,  and  the  last  six  periods  following  the  ingestion  of 
518  grams  of  cooked  oatmeal  and  38  grams  of  butter. 

On  coming  to  the  laboratory,  the  subject  lay  down  on  the  couch  at  7^  47"* 
a.  m.,  and  the  experiment  began  at  8^  17""  a.  m.  In  all  of  the  three  fasting 
periods,  which  were  each  15  minutes  in  length  with  intermissions  of  13  to  14 
minutes,  the  subject  was  reported  as  awake  and  very  quiet.  The  oatmeal  was 
taken  between  9''  40""  and  9*"  55""  a.  m.,  and  the  subject  lay  down  on  the  couch 
again  at  10  a.  m.  The  six  periods  following  the  food  began  at  lO""  13"  a.  m., 
with  intermissions  of  the  usual  length,  except  between  the  last  three  periods, 
these  being  about  an  hour  each.  During  the  fourth,  fifth,  sixth,  and  seventh 
periods  the  subject  was  reported  as  restless,  coughing  and  moving  her  hands 
and  feet.  Between  the  seventh  and  eighth  periods  the  subject  sat  up  in  a 
chair  and  did  not  lie  down  on  the  couch  again  until  about  15  minutes  before  the 
next  period  began.  She  was  much  quieter  in  the  eighth  period  than  previously, 
although  she  reached  once  for  her  handkerchief.  She  felt  sleepy  during  this 
period,  and  took  a  35-minute  nap  between  the  eighth  and  ninth  periods.  The 
results  for  this  experiment  are  given  in  tables  84  and  85. 


STATISTICS    OF    EXPERIMENTS. 


71 


Respiration  Experiment  No.  U8. 

Date,  June  2,  1911.     Body-weight  without  clothing,  37.1  kilos. 

Before  this  experiment,  which  was  the  first  of  Series  II,  the  subject  took 
^V  grain  strychnine.  She  arrived  at  the  laboratory  at  7*^  25™  a.  m.,  without 
breakfast,  and  lay  down  upon  the  couch  at  7''  40™  a.  m.  The  experiment 
began  at  8'^  10™  a.  m.,  continuing  for  two  periods  of  15  minutes  each,  with  an 
intermission  of  12  minutes.  The  subject  was  quiet  throughout  the  experiment, 
with  the  exception  of  a  few  movements  of  the  hands  during  the  second  period. 
The  results  of  the  experiment  may  be  found  in  tables  86  and  91. 

Table  84. — Results  of  respiration  experiment  No.  U7. 


Date  and  time. 

Duration. 

1                       1 
Carbon     !     o               ' 
,^''ox[de     [   „u^^F5i    :  Respinitory!    Average 

1                       1 

Average 

respiration 

rate. 

Apr.  2,  1911: 

Without  food — 

8^  17™  a.m.... 

8  45    a.m. . . . 

9  14    a.m 

7nin.    sec. 

14  58 

15  3 
14    47 

c.c.                 c.c. 

148                  199               0.75                 86 
151        i          203                  .74        1          90 
154        1          213                  .72                 92 

18 
18 
18 

U51        '<        1205        ;          .74        |          89 

18 

VVith  food— 

lOl"  IS^a-m.^... 

10  39    a.m 

11  08    a.m.... 

12  12    p.m 

1  28    p.m.3... 

2  37    p.m.... 

15      3      '          163 

14  58                167 

15  4                177 

14  54                170 

15  6                1.54 
14    49      j          163 

234        !          .70                100 
228        1          .73        i          99 
236                  .75        1          99 
230        1          .74        !          86 
206        !          .75        1          88 
209                  .78        1          92 

18 
19 
19 
19 
19 
18 

■1166                 i2'>i        i            74        1          04 

19 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  without  food,  3.79  c.c;  o.vygen  ab.sorbed  per  Icilo- 
gram  per  minute,  without  food,  5.15  c.c. 

2  Subject  ate  518.4  gms.  cooked  oatmeal  and  38  gms.  butter  between  9'^  40™  and  9**  55™  a.m. 

'Subject  slept  about  35  minutes  after  this  period  and  was  awakened  at  2^  31™  p.m. 

*  Carbon  dio.\ide  eliminated  per  kilogram  per  minute,  with  food,  4.17  c.c;  oxygen  absorbed  per  kilo- 
gram per  minute,  with  food,  5.63  c.c. 

Table  85. — Statistics  of  urine — Respiration  experiments  No.  U7. 


Date  and  period.                        Volume. 

Total 
nitrogen. 

Sugar. 

Apr.  2.1911: 

6'"  40™  a.m.  to    7^  35™  a.m 

7    35    a.m.         9    33    a.m 

9    33    a.m.       11    50    a.m.i 

11    50    a.m.         2    58    p.m 

Apr.  2-3,  1911: 

2'' 58™  p.m.  to    6'^  30™  a.m 

c.c. 
100 
216 
425 
475 

1920 

gms. 

0.42 
.71 
.88 

1.09 

6.73 

gms. 
2.2 
3  7 

10.2 
18.1 

62.8 

•  Subject  ate  518.4  gms.  of  cooked  oatmeal  and  38  gms.  of  butter  between  9^  40™  and  9''  55™  a.m. 
Table  86. — Results  of  respiration  experiment  No.  US. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

June  2,  1911: 

S^  10™  a.m 

8    37    a.m 

7nin.   sec. 
14    56 
14    47 

c.c. 
145 
142 

c.c. 

203 
202 

0.71 
.70 

75 
79 

18 
18 

U44 

1203                  .71 

77                   18         1 

1 

•Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.88  c.c;  oxygen  absorbed  per  kilogram  per  minute  .5.47c. 


72 


METABOLISM    IN    SEVERE   DIABETES. 


Calorimeter  Experiment  No.  U9. 

Date,  June  2, 1911.     Body- weight  without  clothing,  37.1  kilos. 

This  experiment  immediately  followed  respiration  experiment  No.  U7,  and 
was  preceded  by  a  breakfast  of  477  grams  of  oatmeal  and  157  grams  of  heavy 
cream.  She  also  drank  200  c.c.  of  water.  Before  entering  the  bed  calorimeter 
the  subject  urinated  at  9^  30"'  a.  m.  The  experiment  began  at  10^  46""  a.  m. 
and  continued  for  four  45-minute  periods,  ending  at  1^  46"  p.  m.  The  sub- 
ject was  very  quiet,  except  for  several  slight  movements,  reading  until  12''  30°^ 
p.  m.,  when  she  was  reported  asleep  by  the  nurse  in  attendance.  At  I''  16" 
p.  m.  it  was  noted  that  the  subject  was  again  reading.  The  stethoscope  and 
pneumograph  were  used  in  this  experiment,  but,  owing  to  a  loose  adjustment, 
the  records  of  the  respiration  were  unsatisfactory.  The  pulse  records  were 
also  difficult  to  obtain.  The  measurements  of  the  oxygen  indicated  a  leak,  but 
it  was  not  located.  The  measurements  of  the  metabolism  and  other  records 
made  during  the  experiment  are  given  in  tables  87  and  91. 

Table  87. — Measurements  of  metabolism — Calorimeter  experiment  No.  U 9. 


Date  and  period. 


Carbon  dioxide      i 

eliminated.         I  Average 
_[     pulse- 

Per       i     '■^*«'- 
minute,  i 


Total. 


June  2,  1911: 

10*'  40™  a.m.  to  11^  31'°  a.m.'. 

11  31    a.m.       12 

12  16    p.m.         1 
1    01     p.m.         1 

Total,  3  hoursv . 


p.m. 
p.m. 
p.m. 


gms. 
14.6 
15.2 
14.0 
14.5 


c.c. 
166 
171 
158 
164 


58.3 


165 


'  Subject  ate  477  gms.  cooked  oatmeal  and  157  gma.  cream  between  ^^  06"'  and  9*^  25""  a.m. 
-Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.45  c.c. 

Respiration  Experiment  No.  UIO. 

Date,  June  2,  1911.     Body-weight  without  clothing,  36.8  kilos. 

This  respiration  experiment  followed  immediately  after  the  experiment 
with  the  bed  calorimeter  (U9)  and  included  seven  periods,  each  of  which  was 
approximately  15  minutes  long.     The  intermissions  ranged  from  35  minutes  to 

Table  88. — Results  of  respiration  experiment  No.  U 10. 


Date  and  time       ]  Duration. 

eliminated  Jp^bsorbf 
per  minute.  ^     '"'"ui^c. 

Respiratory 
quotient. 

Averasre        Average 

puir^ti.  -p^f- 

June  2, 1911: 

2'^17™p.m.i.... 

3  20    p.m 

4  29    p.m 

5  47    p.m 

6  57    p.m 

8  22    p.m 

9  43    p.m 

Average 

min.  sec. 
14    40 

14  42 

15  2 
14    31 

14  35 

15  2 
15      2 

c.c.                c.c. 

142  207 
147                  204 
141        ;          202 

143  [          202 
140        1          203 

133  200 

134  196 

0.69 
.72 
.70 
.71 
.69 
.67 
.68 

84                   19 
86          1          19 
84                   20 
82          i          20 
84          1          21 
82          !          19 
82          1          20 

2140 

2  202 

69        1          83 

20 

1 

'The  subject  had  eaten  oatmeal  and  cream  between  9^  06™  a.m.  and  9*'  25™  a.m. 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.80  c.c;  oxygen  absorbed  per  kilogram  per  minute,  5.49  c.c. 

1  hour  and  10  minutes.  The  experiment  began  at  2^  17"^  p.  m.  and  ended  at 
9''  58°"  p.  m.  The  subject  was  very  quiet  and  awake  throughout  the  experi- 
ment. A  period  was  begun  in  the  intermission  between  the  first  and  second 
periods,  but  as  the  subject  moved  her  head  and  there  was  the  possibility  of  a 


i 


STATISTICS    OF   EXPERIMENTS. 


73 


leak,  the  measurements  were  discontinued  at  the  end  of  approximately  2 
minutes.  Between  the  second  and  third,  third  and  fourth,  and  the  fifth  and 
sixth  periods  she  sat  up  in  a  chair,  lying  down  on  the  couch  again  13  to  20 
minutes  before  the  beginning  of  the  following  period.  The  nurse  gave  her  a 
massage  in  the  intermission  between  the  fourth  and  fifth  periods.  Previous  to 
the  experiment  the  subject  drank  120  c.c.  of  water.  She  also  urinated  at 
1*"  50™  p.  m.,  and  again  at  5'^  10™  p.  m.,  6*^  40™  p.  m.,  and  10''  30™  p.  m.  The 
results  of  the  experiment  are  given  in  tables  88  and  91. 

Calorimeter  Experiment  No.  Ull. 

Date,  June  2-3,  1911.     Body-weight  without  clothing,  36.2  kilos. 

In  this  experiment  (the  fourth  of  Series  II)  the  subject  remained  in  the 
bed  calorimeter  all  night,  with  one  short  intermission.  At  10  p.  m.  the  nurse  in 
attendance  gave  her  an  alcohol  rub-down  in  preparation  for  the  experiment. 
The  subject  also  drank  a  glass  of  water  at  lO''  50™  p.  m.,  just  before  entering  the 
apparatus,  but  took  no  food.  The  experiment  was  divided  into  two  parts;  the 
first  part  began  at  11''  55™  p.  m.  and  continued  for  one  period  of  1  hour  and  32 
minutes,  and  a  second  of  1  hour  and  47  minutes,  ending  at  2^  14™  a.  m.  The 
subject  was  then  taken  out  of  the  calorimeter  for  a  short  time,  but  returned  to 
the  apparatus  at  2''  40™  a.  m.,  the  second  part  of  the  experiment  beginning  at 
4''  01™  a.  m.     In  this  section  of  the  experiment  the  measurements  were  also 

Table  89. — Measurements  of  metabolism — Calorimeter  experiment  No.  Ull. 


Date  and  period. 


Carbon  dioxide 
eliminated. 


Oxygen  absorbed. 


Total. 


Per 
minute. 


June  2-3,  1911: 

ll''  55™  p.m.  to  l*"  27™  a.m. 
1    27    a.m.      2    14    a.m. 

4  01    a.m.       5    05    a.m. 

5  05    a.m.      6   05    a.m. 

Total  4  hrs.  23  min 


gms. 
24.4 
15.2 
18.3 
15.1 


c.c. 
135 
163 
145 
128 


Total. 


gms. 
23.3 


15.6 


Per 
minute. 


Respi-      Average 
ratory         pulse- 
quotient,       rate. 


73.0 


1141 


38.9 


c.c. 
177 


183 


0.76 

.70 


2  179 


'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.90  c.c. 
-Oxygen  absorbed  per  kilogram  per  minute  (2  hrs.  32  min.),  4.94  c  c. 

made  in  two  periods,  the  first  1  hour  and  4  minutes  and  the  second  1  hour  in 
length.  No  records  of  the  body-temperature  were  obtained,  and  the  pneumo- 
graph was  not  used,  but  the  pulse-rate  was  taken  by  means  of  the  stethoscope. 
The  subject  slept  throughout  the  first  period,  but  waked  at  the  end,  and  her 
slight  movement  at  this  time  disturbecl  the  measurement  of  the  oxygen.  At 
the  beginning  of  the  next  period  she  fell  asleep  again,  and  slept  until  taken  out 
of  the  calorimeter.  After  reentering  the  apparatus  she  slept  the  rest  of  the 
night  and  was  very  quiet.  The  experiment  did  not  appear  to  disturb  the  sub- 
ject at  all,  for  she  was  rested  by  her  night's  sleep  and  said  that  she  had  slept 
better  than  she  did  at  home.  No  water  was  taken  during  the  experiment. 
Urine  was  passed  at  6''  40™  and  lO''  30™  p.  m.  June  2,  and  at  2^  25™  and  Q^  25™ 
a.  m.  June  3.     The  records  of  the  experiment  are  given  in  tables  89  and  91. 

Respiration  Experiment  No.  U  12. 

Date,  June  3,  1911.    Body-weight  without  clothing,  35.8  kilos. 

The  last  experiment  of  Series  II  was  preceded  by  a  breakfast  of  153  grams 
of  beefsteak,  taken  at  7^  42™  a.  m.  With  the  steak,  the  subject  drank  150  c.c. 
of  water.  She  lay  down  upon  the  couch  at  8**  15™  a.  m.,  and  the  experiment 
began  at  8''  41™  a.  m.,  continuing  for  five  periods  13  to  15  minutes  in  length, 
with  intermissions  ranging  from  17  to  45  minutes.     The  subject  complained 


74 


METABOLISM   IN    SEVERE   DIABETES. 


that  the  nosepieces  hurt  her  a  little  m  the  first  period.  In  the  second  she 
moved  rather  more  than  usual,  but  was  quiet  in  the  other  periods.  After  the 
third  period  she  sat  up,  lying  down  again  20  minutes  before  the  fourth  period 
began.  The  subject  urinated  at  10''  17  a.  m.  and  11^  45""  a.  m.  The  results  of 
the  experiment  are  given  in  tables  90  and  91. 

Table  90. — Results  of  respiration  experiment  No.  U 12. 


Date  and  time. 

Carbon 
T>  -  +;„„          dioxide 
Duration,     eij^jn^ted 
per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory     Average 
quotient,      pulse-rate. 

Average 
respiration 

rate. 

June  3,  1911: 

S'' 41"' a. in. I... 
9    20    a.m.... 
9    50    a.m.... 

10  48    a.m 

11  26    a.m.... 

Average 

min.   sec.    \         c.c. 
14    42                140 
12    41       1          165 
12    54      ,          165 
14    35      !          156 
14    20      i          156 

c.r. 
219 

240 
236 

223 

1 

0.64                 88 

.68                 90 

.70                  90 

90 

.70                  91 

21 

22 
23 
21 
21 

1        2  156                2230        I          .68 

i 

90 

22 

I  Subject  ate  153  gms.  of  beefsteak  between  7''  30™  and  7*'  42™  a.m. 

^Carbon  dioxide  eliminated  per  kilogram  per  minute,  4.36  c.c;  oxygen  absorbed  per  kilogram  per  minute,  6.42  c.c. 


Table  91. 


-Statistics  of  urine — Calorimeter  experiments  Nos.  U 9  to  U 11,  and 
respiration  experiments  Nos.  U  8  to  U 12. 


j                1 
Date  and  period.                    Volume.     ™^ity 

Total 
nitrogen. 

Sugar. 

June  1-2,  1011:               ^                          !       c.c. 
7''  00™  p.m.  to    7'*  00™  a.m 1680 

June  2,  1011: 

7'' 00™  a.m.  to    Ol^  30™  a.m.'.. . .         209 

9    30    a.m.         1    50    p.m 782 

1    50    p.m.         5    10    p.m 295 

5  10    p.m.         6    40    p.m 1        118 

0    40    p.m.       10    30    p.m 146 

June  2-3,  1911: 

10*"  30™  p.m.  to    2"  25"' a.m 146 

Junes,  1011: 

2''  2.)™  a.m.  to    6''  25™  a.m 108 

6  25    a.m.       10    17    a.m.2....i        305 
10    17    a.m.       11    45    a.m 81 

1.027 

1.024 
1.018 
1.023 
1.023 

1.022 

1.023 
1.024 
1.034 

gms. 
7.37 

.94 
1.88 
.95 
.49 
.93 

.90 

.68 
1.99 

.82 

gms. 
46.5 

3.9 
18.9 
6  4 
2.3 
1.6 

1.2 

1.4 
5.3 
2  3 

'  Subject  ate  477  gms.  of  cooked  oat:neal  and  157  gms.  of  oreaiii  betw-esn  9"  06  ™  and  9"  25™  a.m. 
2  Subject  ate  153  gnas.  beefsteak  between  7*'  30™  and  7*'  42™  a.m.  and  drank  150  c.c.  of  water. 


Table  92. — Comparison  of  metabolism  experiments  in  the  bed  calorimeter  with  Case  U. 
EXPERIMENTS  WITHOUT  FOOD. 


Experi- 

Weight 

Length 

ment 

Date. 

of 

of  ex- 

No. 

subject. 

periment. 

1911. 

kilos. 

hrs.  7nin. 

U    5 

Mar.   31 

39.9 

1     30 

Ull 

June  2-3 

36.2 

4    23 

Per  minute. 


Carbon  r>„, 


c.c. 
155 
141 


c.c. 
1179 


T?A<,n!-      Average 
"!^P'     I     pulse 
ratory         i" 

quotient.     J^^^^_ 


10.73 


Average 
respira- 
tion per 
minute. 


18.5 


EXPERIMENTS  WITH  FOOD. 


U9 


1911. 
June  2  • 


kilos. 
37  1 


hrs.  Tnin.  I 

3    00     i 


c.c. 
165 


87 


'Oxygen  absorbed  and  respiratory  quotient  for  the  time  included  in  the  periods  11    55™  p.m.  to  l''  27™ 

a.  m   and  5*^  05™  to  O''  05™  a.m. 
2  About  1  hour  30  minutes  before  the  experiment  began  the  subject  ate  477  gms.  of  cooked  oatmeal  and 

157  gms.  cream. 


STATISTICS    OF   EXPERIMENTS. 


75 


CASE  V. 


DESCRIPTION    OF   THE    CASE. 


Male;  born  January  19,  1874;  married;  proprietor  of  a  grocery;  onset  of 
diabetes  July  1909;  sugar  found  in  the  urine  October  1909;  came  under  our 
observation  March  7,  1910;  died  February  6,  1911. 

Family  history. — No  history  of  diabetes  in  the  family.  Father  and  one 
child  well.  Wife  has  had  two  miscarriages.  Mother  ill,  diagnosis  unknown. 
A  brother  is  not  rugged,  and  one  sister  died  of  typhoid  fever. 

Past  history. — The  patient  advanced  slowly  at  school  because  of  "neu- 
ralgia" and  headaches.  Measles,  mAimps,two  attacks  of  diphtheria.  "Inflam- 
mation of  the  gall-duct,"  accompanied  with  severe  pain  but  without  jaundice, 
occurred  three  or  four  times  at  about  32  years  of  age.  At  one  time  consider- 
able alcohoUc  liquor  was  used. 

General  history  of  the  case. — In  July  1909,  polyuria  and  polj^phagia  were 
manifest,  but  polydipsia  did  not  occur  until  October  1909,  when  sugar  was 
found.  The  greatest  quantity  of  urine  reported  was  4,000  c.c.  in  October  1909. 
Weakness,  vertigo,  palpitation,  failing  eyesight,  insomnia,  and  indigestion  were 
the  chief  symptoms.  On  March  8  to  9,  1910,  the  quantity  of  sugar  amounted 
to  115  grams  in  24  hours.  With  a  fairly  rigid  diet  the  patient  did  not  become 
sugar-free,  and,  indeed,  bore  the  restriction  of  diet  very  poorly.  Pneumonia  is 
said  to  have  developed  upon  February  3,  1911;  the  patient  failed  rapidly  and 
death  occurred  February  6,  1911. 

Physical  examination. — Greatest  weight  without  clothing,  63.5  kilos. 
Weight  without  clothing  March  7, 1910,  58.3  kilos.  Height  173  cm.  Tour  de 
taille  72.5  cm.  Pupils  equal  and  reacted  to  light.  Knee-jerks  normal.  No 
edema  of  the  extremities.  Tongue  and  teeth  normal.  No  cervical,  right  axil- 
lary, or  inguinal  gland.  A  left  axillary  gland.  Pulse-rate  76,  regular.  Blood- 
pressure  100.  Heart  and  lungs  not  abnormal.  Abdomen,  nothing  abnormal 
felt. 

Urine  data. — The  urinary  record  is  given  in  table  93.  Throughout  the 
observations  the  urine  was  acid  in  reaction.  No  albumen  was  present,  except 
on  March  27  and  28,  when  there  was  a  very  slight  trace.  Diacetic  acid  was 
also  absent,  except  on  March  8-9,  and  a  very  slight  trace  on  March  28. 


Table  93 

. — Clinical  chart- 

—Case  ^ 

Sugar. 

Date. 

Volume 
of  urine. 

Specific 
gravity. 

Nitrogen. 

Carbo- 
hydrate 
in  diet.* 

NaHCOa 

Body- 
weight 
without 
clothing. 

By  cop- 
per re- 
duction. 

By  rota- 
tion. 

1910. 

c.c. 

gms. 

gms. 

gms. 

gms. 

gms. 

kilos. 

Mar.    8-9 

2300 

1034 

+ 

115 

115 

0 

58.8 

10-11 

2040 

1034 

+ 

82 

5 

59.1 

13-14 

1920 

1031 

+ 

73 

ii5 

2 

58.5 

15-16 

2400 

1028 

»19.3 

+ 

72 

90 

18-19 

1680 

1014 

+ 

7 

50 

3 

58.9 

21-22 

1710 

214.5 

41 

22-232.... 

586 

3.7 

13 

25-26 

2400 

1023 

43 

50 

4 

58.9 

273.... 

750 

1021 

+ 

3 

283.... 

720 

1025 

+ 

3 

28'.... 

1800 

1018 

32 

29".... 

1350 

1016 

8 

303.... 

1920 

1023 

1 

46 

31'.... 

900 

1025 

....               ..         i          16 

1 

'-\mounts  only  approximate. 


2From  G  to  ll*"  15™  a.m.,  Mar.  22. 


3 12-hour  record. 


76 


METABOLISM  IN   SEVERE  DIABETES. 


EXPERIMENTS   WITH   CASE    V. 

Only  one  experiment  was  made  with  this  subject,  the  respiration  apparatus 
being  used.     The  vital  statistics  were  as  follows: 

Date  of  birth,  January  19,  1874;  height,  173  cm.;  body-weight,  without 
clothing,  during  experiments,  60  kilos. 

Respiration  Experiment  No.  VI. 

Date,  March  22,  1910.     Body-weight  without  clothing,  60  kilos. 

The  subject  had  inadvertently  eaten  some  breakfast  at  6''  45'"  a.  m.  on  the 
day  of  the  experiment,  consisting  of  a  2-egg  omelet  and  a  cupful  of  coffee.  He 
arrived  at  the  laboratory  at  8*^  40""  a.  m.,  lay  down  on  the  couch  at  8^'  45'°  a.  m., 
and  the  experiment  began  at  9^  22"^  a.  m.,  continuing  for  five  periods,  with  the 
usual  intermissions.  Two  pneumographs  were  used  to  obtain  the  respiration 
rate  and  the  major  muscular  movements,  and  the  stethoscope  was  employed 

Table  94. — Results  of  respiration  experiment  No.  VI. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

Mar.  22,  1910: 

9''22™a.m.i... 

9    40    a.m 

10  02  a.m.... 
10  27  a.m.... 
10    56    a.m 

min.  sec. 
10    07 
14    50 
14    36 
14    19 
14    24 

c.c. 
222 
204 
198 
204 
195 

c.c. 
285 
291 
283 
274 
280 

0.78 
.70 
.70 
.75 
.70 

69 
68 
66 
66 
66 

11 
12 
15 
13 
15 

S205 

2  283 

.73 

67 

13 

1  Subject  ate  a  light  breakfast  consisting  of  a  2-egg  omelet  and  a  cup  of  coffee  at  d^  45™  a.m. 

'  Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.42  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.72  c.c. 

for  securing  the  pulse-rate.  The  mouth  was  covered  with  surgeon's  plaster  in 
all  the  periods.  Just  before  the  close  of  the  third  period  the  subject  almost 
went  to  sleep.  After  the  experiment  he  said  that  he  found  it  more  difficult  to 
breathe  through  the  apparatus  than  into  the  open  air.  Before  coming  to  the 
laboratory  in  the  morning  he  urinated  at  6  a.  m.,  after  reaching  the  laboratory 
at  8^  45'°  a.  m.,  and  again  after  the  experiment  at  11^  15'°  a.  m.  The  records 
of  the  experiment  may  be  found  in  tables  94  and  95. 

Table  95. — Statistics  of  urine — Respiration  experiment  No.  VI, 


Date  and  period.                    |  Volume. 

I 

Total 
nitrogen. 

Sugar. 

Mar.  22,  1910:              ^                                    c.c. 

le*"  00"  a.m.  to   S""  45°' a.m 151 

8    45    a.m.       11    15    a.m 435 

gms. 
1  16 
2.57 

gms. 
43 
8.7 

'  Subject  ate  a  light  breakfast  consisting  of  a  2-egg  omelet  and  a  cup  of  coffee  at  6^  45™  a.m. 


CASE  W. 

DESCRIPTION    OF   THE    CASE. 


Female;  born  June  1,  1892;  single;  onset  of  diabetes,  November  1908; 
sugar  found  in  the  urine  January  1909;  came  under  our  observation  April  30, 
1910;  condition  November  11,  1912,  comfortable. 


STATISTICS    OF   EXPERIMENTS. 


77 


Family  history.— No  history  of  diabetes  in  the  family.  Father  had  rheu- 
matism. Mother,  three  brothers,  and  five  sisters  are  well.  Two  brothers 
died  of  cholera  infantum;  one  sister  of  spinal  meningitis. 

Past  history. — Measles,  mumps,  chicken-pox.  March  1907,  operation  for 
appendicitis,  with  good  recovery. 

General  history  of  the  case. — In  November  1908  the  patient  was  markedly 
tired,  and  in  January  1909  pruritus  appeared  and  sugar  was  found  in  the  urine. 
In  February  1909  she  suffered  from  periods  of  weakness,  but  was  not  uncon- 
scious. Micturition  was  painful.  Polyuria  and  polydipsia  were  present,  but 
not  polyphagia.  During  the  summer  of  1909  she  suffered  pain  in  the  left  iliac 
fossa,  which  was  constant  in  character  and  accompanied  by  abdominal  tender- 
ness, but  no  fever.  The  pain  was  worse  before  catamenia,  which  was  reported 
as  normal  in  April  1910.  Although  suffering  from  indigestion,  she  vomited  but 
once.  She  was  nervous,  and  complained  of  dizziness,  dyspnea,  and  palpitation. 
August  1909  an  obstruction  Avas  found  in  the  ureter  by  Dr.  Chute.  April  16, 
1912,  the  patient  was  in  comfortable  health. 


Table  96. — Clinical  chart — Case  W. 

Sugar. 

Date. 

Volume 
of  urine. 

Specific 
gravity. 

Nitrogen. 

Carbo- 
hydrate 
in  diet.i 

Carbo- 
hydrate 
balance. 

Body- 
weight 
without 
clothing. 

By  cop- 
per re- 
duction. 

By  rota- 
tion. 

1910. 

c.c. 

gms. 

gms. 

gms. 

gms. 

gms. 

kilos. 

Apr.  29-30 

2000 

1038 

104 

May   9-10 

1023 

20.6 

60.6 

May  10-11 

1170 

1026 

26 

m 

+i45 

60.7 

May  11-12 

1305 

1021 

23 

170 

+145 

59.7 

May  12-13  3.... 

1980 

1017 

8.4 

33 

28 

130 

+  95 

60.1 

May  13-14*.... 

1575 

130 

59  1 

May  14-15 «. . . . 

125 

58.2 

May  15-16'.... 

125 

58.5 

May  16-17 

1440 

1017 

14 

125 

+ii6 

58.5 

May  17-18 

1140 

1021 

8.8 

23 

16 

125 

+100 

58.6 

May  18-19 

1020-f- 

1018 

20.8 

90 

58.8 

May  19-20 

1140 

1015 

8.0 

7 

2 

60 

+  55 

58.9 

May  20-21 

1230 

1015 

tr. 

1 

60 

+  60 

59.0 

May  21-22 

1740 

1010 

8.i 

1 

60 

+  60 

58.6 

May  22-23 

1440 

1014 

8.8 

1 

60 

+  60 

58.5 

May  23-24 

1350 

1014 

9.1 

2 

65 

+  65 

58.9 

May  24-25 

600+ 

1015 

0 

58.7 

June    1-2 

2100 

1035 

62 

Julv    5-6 

1023 

6 

1911. 

Aug.   9-10 

1039 

+ 

26.8 

'  No  sodium  bicarbonate  given  except  8  gms.  on  May  23-24. 


2  Per  cent. 


NH3— N 
•Ammonia,  1.2  gms.;=--— n-:  =11.8  per  cent.       •'Catamenia.  sPer  cent  by  fermentation, 

lotal  JN 

Physical  examination. — Greatest  weight  without  clothing,  63.5  kilos.; 
August  1909,  51.7  kilos.;  April  30,  1910,  61.1  kilos.  Height,  161  cm.  Red 
cheeks.  Pupils  equal  and  reacted  to  light.  Knee-jerks  normal.  No  cervical, 
axillary,  or  inguinal  glands  felt.  Pulse-rate,  112  to  128.  Blood-pressure,  130. 
Heart  13  cm.  to  the  left  of  the  median  line.  No  murmurs.  Lungs  normal. 
Liver  extended  2  fingers'  breadth  below  the  costal  margin.  Spleen  and  kidney 
not  felt.     No  abdominal  tenderness.     Scar  in  appendix  area. 

Urine  data. — The  greatest  quantity  of  urine  recorded  was  in  July  1909 
i.  e.,  4500  c.c.  The  urinary  record  during  observation  is  given  in  table  96. 
Throughout  this  period  the  reaction  was  acid,  with  an  occasional  slight  trace 
of  albumen.  Diacetic  acid  was  not  present.  The  sugar  in  the  urine  decreased 
rapidly  with  moderate  restriction  of  the  diet,  and  disappeared  Avithin  three 
weeks.  A  subsequent  report,  however,  showed  a  return  of  sugar  a  few  months 
later.    Sodium  bicarbonate  was  given  only  once — 8  grams  on  May  23-24, 1910. 


78 


METABOLISM   IN    SEVERE   DIABETES. 


EXPERIMENTS   WITH    CASE    W. 

Two  respiration  experiments  were  made  with  this  subject,  in  both  of 
which  she  fasted.     The  vital  statistics  were  as  follows: 

Date  of  birth,  June  1,  1892;  height,  161  cm.;  range  of  body-weight 
without  clothing  during  experiments,  58.9  to  60.1  kilos. 

Respiration  Experiment  No.  Wl. 

Date,  May  13, 1910.     Body-weight  without  clothing,  60.1  kilos. 

The  subject  came  to  the  laboratory  fasting  at  7^  45°"  a.  m.,  and  lay  down 
upon  the  couch  at  7''  55"'  a.  m.  The  experiment  began  at  8*"  07'"  a.  m.,  con- 
tinuing for  four  periods  of  10  to  11  minutes  each,  with  intermissions  of  10  to  14 
minutes.  The  subject  was  nervous  throughout  the  whole  experiment,  espe- 
cially in  the  last  period;  the  respiration  was  consequently  irregular.  At  the 
close  of  the  second  period  she  said  that  her  nose  felt  as  if  it  were  bleeding.  Just 
after  the  beginning  of  the  third  period  she  opened  her  mouth.  After  the  exj^eri- 
ment  was  over  the  subject  felt  a  little  faint.  She  seemed  to  breathe  easily 
through  the  nose,  and  but  for  the  nervousness  was  a  very  good  subject.  The 
records  of  the  experiment  are  given  in  table  97. 

Table  97. — Results  of  respiration  experiment  No.  W 1. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

1                       i 

abs'^rbTd    1  Respiratory;    Average 
per  minute.     <i^°^'^^^-      Pu'se-rate. 

i 

Average 

respiration 

rate. 

May  13.  1910: 

%^  07™  a.m 

8    28    a.m 

8  53    a.m 

9  13    a.m 

viin.  sec. 
10    24 
10    39 
10    17 
10    27 

c.c. 
171 
170 
161 
165 

1 
c.c.         I 

238  0.72 
228        [          .75 

239  ;          .69 

110 

100 
106 
100 

18 
16 
16 
16 

1167                »2.'?.'5 

.72 

104 

17 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.78  c.c;  oxygen  absorbed  per  kilogram  per 
minute,  3.91  c.c.  The  urine  collected  between  7  and  10"  10™  a.m.  amounted  to  197  c.c.  and 
contained  0.94  gm.  nitrogen  and  1.6  gms.  sugar. 

Respiration  Experiment  No.  W2. 

Date,  May  24,  1910.     Body-weight  without  clothing,  58.9  kilos. 

This  was  also  a  fasting  experiment,  the  subject  having  taken  no  food  since 
the  evening  meal  of  the  day  before.  She  arrived  at  the  laboratory  at  8''  IS"' 
a.  m.,  lay  down  on  the  couch  at  8''  30'"  a.  m.,  and  the  experiment  began  at 
8^  43"*  a.  m.,  continuing  for  three  10-minute  periods,  with  intermissions  of  11 
to  14  minutes.  She  was  not  nearly  so  nervous  as  in  the  previous  experiment, 
but  as  the  periods  continued  became  more  restless,  and  at  the  close  of  the  last 
period  felt  faint.     The  results  of  the  experiment  are  given  in  table  98. 

Table  98. — Results  of  respiration  experiment  No.  W  2. 


Date  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 

respiration 

rate. 

May  24,  1910: 

8^43™  a.m 

9    07    a.m 

9    28    a.m 

Average 

min.   sec. 
10      0 
9    40 
9    53 

c.c. 
157 
160 
164 

c.c. 
207 
219 

0.76 
.73 

•• 

91 
91 
99 

16 
16 
16 

'160 

1213 

.75 

94 

16 

1  Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.72  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  3.62  c.c. 
The  urine  collected  between  7  and  9"  45™  a.m.  amounted  to  162  c.c.  and  contained  0.57  gm.  nitrogen  and  0.1  gm.  sugar. 


STATISTICS   OF   EXPERIMENTS. 


79 


CASE  X. 


DESCRIPTION    OF   THE    CASE. 

Male;  born  October  1875;  married;  clerk  in  grocery  store;  onset  of  dia- 
betes, July  1908;  sugar  found  in  urine  September  1908;  came  under  our  obser- 
vation, February  28,  1910;  condition.  May  8,  1912,  comfortable. 

Family  history. — No  history  of  diabetes  in  the  family.  Father,  mother, 
three  brothers,  four  sisters,  and  one  child  well.  A  brother  and  a  sister  died 
soon  after  birth. 

Past  history.— Me&sles,  mumps,  whooping-cough,  jaundice  at  8  or  10 
years  of  age.  Twelve  years  and  three  years  previous  to  observation,  there  was 
a  swelling  in  the  right  knee  for  periods  of  6  weeks  and  10  days,  respectively. 

Table  99. — Clinical  chart — Case  X. 


Date. 


1910. 
Feb.  27-28  2  .... 
Feb.  28-Mar.  1 ' 
Mar.     1-2 

Mar.     2-3 

Mar.     3-4 

Mar.     4-  5 

Mar.     5-6 

Mar.     6-7 

Mar.     7-8 

Mar.     8-9 

Mar.     9-10 

Mar.  10-11 

Mar.  11-12 

Mar.   12-13 

Mar.   13-14 

Mar.  14-15 

Mar.   15-16 

Mar.  16-17 

Mar.  17-18 

Apr.     3-4 

Apr.    10-11 

Apr.    14-15 

May     4-  5 

Oct.    23-24 

Dec.     1-2 

1912. 
Apr.    26-27 


6 
a 

3 

i 

1 

a 
1 

■a 
'S 

C3 
o 

s 

1 

c.r. 

gms. 

2850 

1039 

0 

25.9 

2625 

1041 

0 

23.8 

1740 

1042 

0 

20.7 

2070 

1040 

0 

22.9 

2565 

1038 

0 

1890 

1033 

0 

2115 

1029 

0 

1650 

1030 

0 

1455 

1031 

S1.+ 

1530 

1027 

S1.+ 

2070 

1023 

0 

1710 

1023 

0 

1200 

1026 

S1.+ 

11.0 

1620 

1021 

0 

12.9 

1770 

1017 

0 

11.3 

2280 

1020 

0 

12.8 

2640 

1025 

0 

12.9 

2670 

1019 

0 

19.3 

1730 

1017 

0 

13.0 

1029 

0 

1470 

0 

2000 

1023 

0 

1625 

1028 

0 

720 

1028 

625 

1028 

S1.+ 

1750 

1028 

+ 

Sugar. 


gms. 
209 
182 
109 
124 


194 
179 
101 

116 
133 
49 
72 
36 
38 
28 
21 
17 


«0.8 


39 


Diet.i 


rfl    -g 


115 

115 
115 
15 
75 
50 
50 
35 
25 
20 
15 
15 
15 
15 
15 
15 
15 
15 


+  5 
-10 
-20 
-35 
+  5 
+  15 
+10 
+  5 
+  5 
+  5 
+  5 
+10 
+10 
+10 
+15 
+10 
+10 


+10 

+20 
-15 


■S.S 


m 


kilos. 
62.3 
62.3 
62.7 
63.1 
62.3 
63.0 
62.8 
63.1 
63.2 
63.6 
63.4 
63.1 
63.6 
64.0 
63.4 
64.4 
64.7 
64.6 

64!6 
65.5 


70.9 
70.9 


1  No  sodium  bicarbonate  was  given,  except  15  gms.  on  Mar.  14-15  and  15-16. 

NH3— N  y, 

2  Ammonia,  1.9  gms.;  ^  ,^  ,  ^^  =6.0  per  cent.         'Period  was  22|  hrs, »'.  e.,  8"  15"  to  7  a.m. 


*  Per  cent. 


Total  N 
^  Less  than  0.1  per  cent. 


The  patient  used  considerable  tobacco  and  ate  excessively  of  candy  and  cookies, 
both  in  the  grocery  store  and  at  home.  Ten  years  previous  to  observation 
considerable  alcoholic  liquor  was  used. 

General  history  of  the  case. — While  the  onset  of  the  diabetes  was  in  July 
1908,  the  disease  first  attracted  particular  attention  and  was  diagnosed  in 
September  1908,  because  of  polyuria  at  a  horse-race.  5000  c.c.  of  urine  were 
voided  during  the  night  at  the  onset.  Other  symptoms  were  polydipsia,  poly- 
phagia, weakness,  loss  of  weight,  a  parched  tongue,  pain  in  the  back,  extreme 
constipation,  impotence,  and  failing  eyesight.  Under  the  advice  of  his  physi- 
cian the  patient  ate  no  pork,  fat,  or  vegetables,  but  drank  skim  milk! 

The  unusually  favorable  course  of  the  case,  despite  the  unpromising  con- 
dition of  the  patient  when  first  seen,  is  probably  due  to  the  change  in  diet,  as 


80 


METABOLISM  IN   SEVERE   DIABETES. 


prior  to  the  time  of  observation  his  diet  had  been  unfortunate.  The  case  illus- 
trates the  unreliabihty  of  prognosis  without  repeated  observations  upon  the 
same  patient. 

Physical  examination. — Greatest  weight  without  clothing,  90.7  kilos.; 
July  1908,  85.3  kilos.;  February  23,  1910,  64.5  kilos.  Height,  170  cm.  Tour 
de  taille,  76  cm.  Pupils  equal  and  reacted  to  light.  Knee-jerks  normal.  No 
edema  of  extremities.  A  few  small  left  axillary  glands.  No  acetone  odor  to 
breath.  One-third  of  the  teeth  missing.  Lungs  and  heart  normal.  Pulse-rate, 
80.  Blood-pressure,  90  (two  estimations,  Riva  Rocci).  Abdomen,  nothing 
abnormal  felt. 

Urine  data. — ^The  urinary  record  for  the  period  of  observation  is  given  in 
table  99.  The  reaction  was  acid  throughout,  except  March  14-16, 1910,  when 
it  was  alkaline.  There  were  occasional  slight  traces  of  albumen.  The  quan- 
tity of  sugar  in  the  urine  on  February  27-28,  1910,  amounted  to  209  grams  in 
24  hours,  and  the  ammonia  to  1.9  grams.  Under  strict  dieting,  sugar  disap- 
peared from  the  urine  after  12  days  and  the  urine  was  sugar-free  on  December 
1,  1910,  the  weight  having  risen  to  71  kilos.  No  sodium  bicarbonate  was 
given  the  patient,  except  15  grams  on  both  March  14  and  March  15.  On  April 
26,  1912,  the  quantity  of  sugar  reached  39  grams  in  24  hours,  and  there  was  a 
trace  of  diacetic  acid.  The  patient  reported  having  successfully  withstood  an 
attack  of  pleurisy,  and  that  the  6.8  kilos,  of  weight  lost  during  that  illness  had 
been  regained. 

EXPERIMENTS  WITH  CASE  X. 

With  this  subject  3  calorimeter  experiments  were  made,  in  all  of  Avhich  the 
chair  calorimeter  was  used.  The  third  experiment  was  preceded  by  a  respira- 
tion experiment.  No  food  was  taken  in  any  of  the  experiments,  and  a  fast  of  at 
least  12  hours  preceded  them.  A  comparison  of  the  results  obtained  in  the 
calorimeter  experiments  is  given  in  table  107.  The  vital  statistics  of  the  sub- 
ject were  as  follows: 

Date  of  birth,  October  1875;  height,  170  cm.;  range  in  body- weight  -with- 
out clothing  during  the  experiments,  62.3  to  64.6  kilos. 

Table  100. — Measurements  of  metabolism — Calorimeter  experiment  No.  XI. 


Date  and  period. 

Carbon  dioxide        n^,„^„  „Uc«,k„j 
eUminnted.        1  Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 

minute. 

Total.      JZt.. 

Feb.  28, 1910: 

lO*"  10"  a.m.  to  ll''  lO""  a.m 

11  10    a.m.       12    10    p.m 

12  10    p.m.         1    10    p.m 

gms. 
27.6 
24.8 
25.4 

1 
c.c.            gms.            c.c.       \ 
234            27.4              320            0.73 
211            24.7              288              .73 
215      1      24.9              290              .74 

70 
68 
66 

22 
22 
20 

TotalShrs.i 

77.8 

220              77  n                2Qfl       ! 

-        1 

1 

1 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,3. 53  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.80  c.c. 

Calorimeter  Experiment  No.  XI. 

Date,  February  28,  1910.    Body-weight  without  clothing,  62.3  kilos. 

The  subject  came  to  the  laboratory  without  breakfast  at  8^  lO'"  a.  m. 
and  entered  the  chair  calorimeter  at  8^  41"  a.  m.  The  experiment  began  at 
10'^  lO""  a.  m.,  and  continued  for  three  1-hour  periods,  ending  at  1''  lO'"  p.  m. 
Records  of  the  pulse  and  respiration  rates  were  obtained  by  means  of  the  steth- 
oscope and  pneumograph,  while  body-temperature  records  were  secured  with 


i 


STATISTICS   OF   EXPERIMENTS. 


81 


the  rectal  thermometer.  The  subject  also  used  a  clinical  thermometer  at 
11^  10'°  a.  m.,  12'^  lO""  p.  m.,  and  1^  10™  p.  m.  In  this  and  the  succeeding 
experiments  an  attempt  was  made  to  obtain  some  record  of  the  muscular 
activity  of  the  subject  by  the  use  of  a  pneumatic  cushion  connected  with  a 
kymograph.  Throughout  the  experiment  there  was  but  little  muscular  move- 
ment aside  from  the  activity  incidental  to  telephoning  several  times  during 

Table  101 . — Statistics  of  urine — Calorimeter  experiment  No.  X 1 . 


Date  and  period. 

Volume. 

Total 
nitrogen. 

Sugar. 

Feb.  28,  1910:  S''  15"  a.m .  to  l''  20"  p.m 

Feb.  28  to  Mar.  1,  1910:  l*"  20"  p.m.  to  7  a.m. . . 

c.c. 

227 
2400 

gms. 
3.43 

.... 

gma. 

8.9 

182.1 

each  period,  and  drinking  64  c.c.  of  water  at  lO""  20°^  a.  m.  Previous  to  the 
experiment  the  subject  urinated  and  defecated  at  8*^  15"  a.  m.,  and  urinated 
again  at  1^  20™  p.  m.  after  the  experiment  was  over,  but  was  unable  to  urinate 
during  the  experimental  period.  The  records  of  the  experiment  are  given  in 
tables  100  and  101. 


Table  102. — Measurements  oj  metabolism — Calorimeter  experiment  No.  X2. 


Date  and  period. 

^^SS^nSl'^        Cygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

mEute.       Total. 

Per 

minute. 

Mar.  1.1910: 

igl"  18"  a.m.  to  lO''  18"  a.m 

10  18    a.m.       11    18    a.m 

11  18    a.m.       12    18    p.m 

Total  3  hrs.2 

gma. 
24.2 
24.5 
23.5 

c.e.            gma. 
205           20.3 
208           23.0 
199            22.5 

c.c. 
236 
268 
262 

0.87 
.78 
.76 

67 
63 
59 

21 
20 
21 

72.2 

204           65.8 

256 

>  Subject  drank  a  cup  of  cofifee  about  2  hours  before  the  experiment  began. 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,  3.25  c.c;  oxygen  absorbed  per  kilogram  per  minute,  4.08  c.c. 

Calorimeter  Experiment  No.  X2. 

Date,  March  1,  1910.     Body-weight  without  clothing,  62.7  kilos. 

With  the  exception  of  a  cup  of  coffee,  no  food  was  taken  by  the  subject 
before  he  came  to  the  laboratory  at  7^  50™  a.  m.  At  ^^  08™  a.  m.,  the  subject 
entered  the  chair  calorimeter;  the  experiment  began  at  9^  18™  a.  m.,  continued 
for  three  1-hour  periods,  and  ended  at  12^  18™  p.  m.  The  records  of  the  pulse 
and  respiration  rates  were  obtained  as  in  the  preceding  experiment,  but  the 
rectal  thermometer  was  not  used,  although  records  were  taken  by  the  subject 
with  a  clinical  thermometer  at  ^^  28™  a.  m.,  10^  32™  a.  m.,  11"^  28™  a.  m.,  and 

Table  103. — Statistics  of  urine — Calorimeter  experiment  No.  X2. 


Date  and  period. 


Mar.  1,1910:                .  ex. 

i7'^00"a.m.  to   9°  28"  a.m 143 

9    28    a.m.       10    32    am 58 

10  32    a.m.       11    35    a.m 48 

11  35    a.m.       12    25    p.m 37 

Mar.  1-2,  1910:              ,                           \  ,.„ 

12'' 25"  p.m.  to   7'' 00"  a.m i  1455 


Volume. 


Total 
nitrogen. 


gm*. 

1.90 
.77 
.66 
.56 

16.78 


Sugar. 


gms. 
9  8 
3.1 
2  1 
1.3 


'Subject  drank  a  cup  of  coffee  at  about  7^  15™  (?)  a.m. 


82 


METABOLISM   IN    SEVERE   DIABETES. 


12''  18"'  p.  m.  Near  the  end  of  the  first  period  the  subject  was  asleep,  waking 
just  after  the  beginning  of  the  second  period.  He  telephoned  once  in  each 
period.  The  subject  urinated  before  coming  to  the  laboratory  at  7  a.  m.,  and 
three  times  during  the  experiment,  i.  e.,  at  9^'  28™  a.  m.,  10*^'  32™  a.  m.,  and 
11''  35™  a.  m.,  also  at  12''  25™  p.  m.,  after  the  experiment  was  over.  He  drank 
no  water.     The  records  of  the  experiment  are  given  in  tables  102  and  103. 

Respiration  Experiment  No.  X3. 

Date,  March  17,  1910.     Body-weight  ^vithout  clothing,  64.6  kilos. 

On  the  experimental  day  the  subject  drank  a  cupful  of  coffee  before  com- 
ing to  the  laboratory',  but  ate  no  breakfast.  He  reached  the  laboratory  at 
7''  40™  a.  m.,  lay  clown  on  the  couch  at  7''  45™  a.  m.,  and  the  experiment  began 
at  8''  58™  a.  m.  The  three  periods  ranged  from  12  to  15  minutes  in  length,  with 
intermissions  from  8  to  10  minutes,  the  last  period  ending  at  9''  56™  a.  m. 
After  the  experiment  began  the  subject  breathed  slower  and  possibly  deeper 
than  he  had  previously.  In  the  second  period  he  took  several  very  deep 
breaths.  In  this  period,  also,  there  was  a  slight  leak  in  the  nosepiece,  and  a 
new  nosepiece  was  accordingly  used  for  the  next  period.  Immediately  after 
the  experiment  was  over  the  subject  urinated  at  9*'  56™  a.  m.,  the  last  period 
being  shortened  on  account  of  the  pressure  of  urine.  The  records  of  the  experi- 
ment are  given  in  tables  104  and  106. 

Table  104. — Results  of  respiration  experiment  N^o.  X3. 


Date  and  time. 

Duration. 

Carbon 

dio-xide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

1 

Respiratory!    Average 
quotient.    !  pulse-rate. 

Average 

respiration 

rate. 

Mar.  17,  1910: 

1 S*"  58™  a.m 

9    22    a.m 

9    44    a.m 

min   sec. 
14    54 

14    42 
12    23 

c.c. 
178 
179 
189 

c.c. 
247 
245 
243 

0.72                 72 
.73                 73 
.78                72 

11 
16 
15 

182                  245        1        0.74        !          72          !          14          1 

; 

1 

'Subject  drank  a  cup  of  coffee  about  If  hours  before  experiment  began. 

2  Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.82  c.c;  oxygen  absorbed  per  kilogram  per  minute,  3.79  c.c. 

Calorimeter  Experiment  No.  X4. 

Date,  March  17,  1910.     Bodj^-weight  without  clothing,  64.6  kilos. 

This  experiment  was  preceded  by  a  five-period  respiration  experiment 
(experiment  No.  X3).  The  subject  drank  a  cupful  of  coffee  on  the  morning 
of  the  experimental  daj',  but  aside  from  this  took  no  food  after  the  evening 
meal  of  the  day  before.  He  entered  the  chair  calorimeter  at  10''  08™  a.  m.; 
the  experiment  began  at  10''  45™  a.  m.,  continued  for  three  1-hour  periods, 
and  ended  at  l''45™p.  m.     The  rectal  thermometer  was  not  used,  but  the 

Table  105. — Measurements  of  metabolism — Calorimeter  experiment  No.  X4- 


Date  and  period. 

Carbon  dioxide 
eliminated. 

Oxygen  absorbed. 

Respi- 
ratory 
quotient. 

Average 
pulse- 
rate. 

Average 
respira- 
tion rate. 

Total. 

Per 
minute. 

Total. 

Per 
minute. 

Mar.  17,  1910: 

10''  45™  a.m.  to  ll*"  45™  a.m 

11  45    a.m.       12    45    p.m 

12  45    p.m.         1    45    p.m 

Total  3  hrs.i 

gms. 
20.9 
23.1 
22.9 

c.c. 
177 
196 
194 

gms. 
17.5 
22.8 
19.9 

c.c. 
204 
266 
232 

0.87 
.74 
.84 

69 

70 
71 

19 
20 
20 

66.9 

189 

60.2 

234      '                  <                  1                  1 

1 

'Carbon  dioxide  eliminated  per  kilogram  per  minute,  2.93  c.c. ;  oxygen  absorbed  per  kilogram  per  minute,  3.62  c.c. 


STATISTICS   OF   EXPERIMENTS. 


83 


pulse  and  respiration  records  were  taken  in  the  usual  way.  By  means  of  the 
clinical  thermometer  the  subject  made  a  few  records  of  the  body  temperature 
at  10»^  55"  a.  m.,  ll^^  55'"  a.  m.,  12''  55"^  p.  m.,  and  1'^  50™  p.  m.  During  the 
latter  part  of  the  second  period  the  subject  was  apparently  asleep,  and  was 
sound  asleep  near  the  end  of  the  third  period,  but  awoke  before  the  close  of  the 

Table  106. — Statistics  of  urine — Respiration  experiment  No.  X3  and  calorimeter 

experiment  No.  X4- 


Date  and  period. 

Volume. 

Total 
nitrogen. 

Sugar. 

Mar.  17.  1910: 

7^  00°^  a.m.  to  ^^  55™  a.m.i 

9    55    a.m.       1    00    p.m 

c.c. 
627 
142 

960 

gms. 
1.61 
1.09 

10.38 

gms. 

0.5 

.2 

2.1 

Mar.  17-18,  1910: 

l''  00"  p.m.  to  1^  00™  a.m 

'Subject  drank  a  cup  of  coffee  at  about  7*'  15™  (?)  a.m. 

experiment.  He  telephoned  twice  during  each  period.  Before  the  experiment 
he  urinated  at  9''  55™  a.  m.,  but  was  unable  to  urinate  again  until  1  p.  m.  No 
water  was  taken  during  the  experimental  period.  The  records  of  the  experi- 
ment are  given  in  tables  105  and  106. 

Table  107. — Comparison  of  metabolism  experiments  in  the  chair  calorimeter  with  Case  X. 

Experiments  without  food. 


F.xperi- 
ment 
No. 

Date. 

Weight 

of 
subject. 

Length  of 
experiment. 

Per  minute. 

Respi- 
ratory 
quotient. 

Average 
pulse  per 
minute. 

1 

Average 
respiration 
per  minute. 

Carbon 

dioxide 

eliminated. 

Oxygen 
absorbed. 

XI 
X2 
X4 

1910. 
Feb.  28.... 
Mar.   P... 
Mar.  17.... 

kilos. 
62.3 
62.7 
64.6 

hrs.   min. 
3      00 
3      00 
3      00 

c.c. 
220 
204 
189 

c.c. 
299 
256 
234 

0.73 
.80 
.81 

68 
63 
70 

21.5 
20.5 
19.5 

'About  2  hours  before  the  experiment  began  the  subject  drank  a  cup  of  coffee. 


PART   III. 

DISCUSSION  OF  RESULTS  AND  GENERAL  CONCLUSIONS. 

While  in  general  the  order  and  method  of  discussion  of  the  subjects  in  this 
publication  follow  that  in  the  earlier  report,  as  experimental  evidence  accumu- 
lated certain  topics  which  were  much  more  completely  studied  warranted  more 
extensive  consideration.  Furthermore,  while  in  the  earlier  publication  it  was 
important  to  emphasize  more  especially  the  relationship  between  the  respira- 
tory exchange  and  the  character  of  the  metabolism,  particularly  with  normal 
individuals,  here  it  is  necessary  to  pay  but  Httle  attention  to  normal  metabo- 
lism, because  it  is  believed  that  this  phase  of  the  study  was  amply  treated  in  the 
earlier  report.  None  of  the  experiments  with  food  are  discussed  in  this  report 
pending  further  investigation,  but  the  statistics  for  these  experiments  have  been 
presented  in  order  to  record  the  data  permanently  for  subsequent  use. 

Pulse-Rate. 

In  the  earlier  series  of  experiments  a  cursory  examination  of  the  pulse-rate 
taken  from  time  to  time  indicated  that  there  was  apparently  no  marked  differ- 
ence between  the  pulse-rate  of  normal  individuals  and  that  of  diabetics,  the 
fluctuations  in  the  pulse-rate  of  the  diabetic  subjects  being  within  normal 
limits.  It  would  appear  from  the  lack  of  data  upon  the  subject  in  the  text- 
books of  medicine  and  in  the  monographs  upon  diabetes  mellitus  that  this 
coincides  with  the  opinion  of  most  clinicians,  but  such  a  conclusion  rests  upon 
negative  evidence  alone,  since  usually  little  attention  is  paid  to  the  pulse-rate 
in  chronic  afebrile  diseases  of  a  non-circulatory  type.  It  is  quite  possible  that 
a  closer  study  of  this  factor  may  supply  much  information  of  value. 

In  physiological  experimentation  it  is  frequently  difficult  to  distinguish 

between  the  normal  and  the  abnormal.     The  popular  conception  of  a  normal 

pulse-rate  is  the  observation  usually  made  by  a  physician  in  his  office,  which 

may  often  be  affected  by  the  muscular  exercise  of  the  patient  in  walking  to  the 

office,  or  the  excitement  incidental  to  consulting  a  physician.     To  obtain  a 

true  normal  value,  however,  the  observation  should  be  made  under  conditions 

which  would  insure  its  being  unaffected  by  food,  exercise,  or  mental  stimulus 

of  any  kind.     Such  conditions  are  obtained  when  the  record  is  taken  with  the 

subjects  lying  quietly  in  bed  without  food.     It  seemed  therefore  desirable  in 

the  later  researches  to  make  a  more  detailed  record  of  these  values,  and  study 

carefully  not  only  the  pulse-rate  of  the  diabetic  subjects,  but  also  of  the  normal 

subjects  used  for  comparison.     An  abstract  of  the  results  is  presented  in  tables 

108  and  109,  in  which  are  given  the  minimum  and  maximum  pulse-rates 

recorded  while  the  subjects  lay  quietly  without  food  in  the  bed  calorimeter  or 

on  a  couch  in  respiration  experiments.     The  values  given  for  the  diabetics 

include  those  obtained  for  all  of  the  subjects  in  both  the  earlier  and  the  later 

experiments,  with  the  exception  of  E  and  F,  no  records  of  pulse-rate  being 

available  which  were  taken  while  these  subjects  were  lying  down. 

85 


86 


METABOLISM   IN    SEVERE   DIABETES. 


The  average  for  all  of  the  diabetic  subjects  shows  a  minimum  pulse-rate  of 
65  beats  per  minute,  and  a  maximum  of  81  beats.  The  average  maximum  and 
minimum  pulse-rates  for  the  normal  subjects  are  54  and  74  respectively,  both 
materially  lower  than  the  averages  found  for  the  diabetic  subjects.  In  prepar- 
ing these  tables,  care  v/as  taken  not  to  include  any  records  obviously  affected 
by  excitement  or  other  untoward  incident  in  connection  with  the  experiment, 
three  records  approximately  constant  usually  being  taken  as  indicating  the 
maximum  or  minimum.  The  values  given  can  therefore  be  considered  as  repre- 
senting the  average  normal  variations  in  pulse-rate  to  be  expected  for  normal 
Table  108. — Pulse-rate  of  diabetic  subjects. 


Subject. 

Minimum. 

Maximum. 

Subject. 

Minimum. 

Maximum. 

Subject. 

Minimum. 

Maximum. 

A 

65 
56 
50 
52 
69 
64 

n7 

60 

86 
72 
84 
58 
74 
90 
122 
84 

1 
K 

73 
54 
64 
53 
57 
64 
61 
64 

83 
73 
80 
84 
69 
82 
83 
73 

S 

57 
63 
72 
62 
90 
72 

60 
71 
97 
69 
111 
75 

B 

L 

T 

c 

M 

U 

D 

N 

V 

G 

0 

W 

H 

P 

X  

T 

o 

J 

R.::::::::: 

Average  . 

65 

81 

individuals  under  the  conditions  of  experimenting  as  employed  in  this  labora- 
tory, and  for  patients  with  severe  diabetes.  It  will  be  seen,  therefore,  that  both 
the  minimum  and  maximum  pulse-rates  of  normal  individuals  are  markedly 
lower  than  those  of  diabetics. 

It  must  furthermore  be  remembered  that  in  practically  every  instance  the 
normal  individual  led  a  much  more  active  life,  had  much  greater  muscular  tone, 
and  was  more  restless  than  were  the  diabetics.  This  makes  the  difference  in 
pulse-rate  all  the  more  striking,  since  one  would  ordinarily  expect  a  somewhat 
higher  value  with  the  more  active  and  restless  normal  subjects  than  with  the 

Table  109. — Pulse-rale  of  normal  subjects. 


Subject. 

Min. 

Max. 

Prof.C 

48 
54 
48 
50 
55 
74 
48 

63 
79 
80 
68 
74 
97 
72 

Miss  L 

V.  G 

M.B 

H.B.L 

MissB.  W 

D.M 

Total  average.. 

54 

74 

Subject. 

Min. 

Max. 

A.  F.  G 

59 
56 
56 
61 
74 
58 
54 
46 
53 

62 
82 
73 
75 
90 
70 
96 
76 
66 

T.M.C 

MissE.  W 

Mrs.  S.  C 

H.H.  A 

S  A.  R 

Dr.  P.  R 

Subject. 

Min. 

Max.    1 

1 

C.  H.  H 

53 
49 
70 
50 
37 
45 
40 
52 
49 

69 
82 
82 
61 
64 
59 
62 
74 
66 

M.  A.  M 

MissB 

Dr.  S 

H.  F.  T 

E.  P.  C 

K.H.A 

J.  R 

0.  F.  M 

weak,  sick  diabetics,  disinclined  to  any  extraneous  muscular  motion.  An 
examination  of  tables  108  and  109  shows  no  regularity  in  either  the  minimum 
or  maximum  pulse-rates  when  individual  diabetics  are  compared  with  normal 
individuals,  since  some  of  the  diabetic  subjects  show  a  minimum  pulse-rate  con- 
siderably lower  than  the  average  minimum  pulse-rate  of  the  normal  subjects; 
and  similarly,  the  normal  individuals  in  some  instances  show  a  pulse-rate  con- 
siderably higher  than  the  average  maximum  pulse-rates  of  the  diabetics.  On 
the  whole,  however,  a  distinct  tendency  toward  an  increased  pulse-rate  in 
diabetics  is  here  clearly  shown.     This  increase  is  fully  in  conformity  with  the 


DISCUSSION    OF   RESULTS   AND    GENERAL    CONCLUSIONS.  87 

increased  metabolism  previously  noted  and  further  substantiated  by  the  evi- 
dence set  forth  in  this  report.  Yet  in  this  discussion  of  the  pulse-rate  it  should 
be  stated  that  it  is  questionable  whether  sufficient  information  with  regard  to 
normal  pulse-rate  has  accumulated  to  indicate  that  a  variation  above  normal 
of  15  per  cent  could  be  recognized.  While  the  metabohsm  may  be  15  per  cent 
above  normal  and  be  accurately  measured,  since  normal  metabolism  is  fairly 
well  estabhshed,  a  15  per  cent  increase  in  pulse-rate  could  not  be  so  easily 
identified.  The  intimate  relationship  between  pulse-rate  and  metabohsm  is 
increasingly  evident  in  practically  every  new  publication  on  metabolism  and 
shows  that  to-day  the  pulse-rate  is  taking  on  a  new  significance;  it  is  not  at  all 
impossible  that  the  degree  of  acidosis  and  the  degree  of  metabolism  may  be  at 
least  approximately  estimated  in  diabetics  by  a  careful  examination  of  the 
pulse-rate.  In  this  connection,  a  reference  to  the  later  discussion  on  the  rela- 
tionship between  acidosis  and  metabolism  will  be  of  interest.  (See  page  123.) 
While  an  increased  pulse-rate  is  invariabh^  accompanied  by  an  increased 
metabolism,  it  is  by  no  means  to  be  inferred  that  the  increased  metabohsm  is 
due  exclusively  to  the  work  of  the  heart.  In  fact,  from  what  is  known  of  the 
work  of  the  heart,  it  can  be  seen  that  probably  but  a  very  small  proportion 
of  the  total  increase  can  be  properly  ascribed  to  the  actual  muscular  action  of 
the  heart  itself,  but  that  the  increased  pulse-rate  is  an  excellent  index  of  gen- 
eral tonus  is  highly  probable.  Unquestionably,  during  increased  metabolism 
and  increased  pulse-rate,  there  is  some  tendency  toward  an  increased  respira- 
tion rate,  but  here  again  it  is  highly  improbable  that  the  muscular  action 
involved  in  raising  the  chest-wall  can  in  any  considerable  proportion  account 
for  the  total  increase  in  metabolism.  On  the  other  hand,  both  the  increased 
muscular  activity  of  the  heart  and  the  increased  work  of  the  respiratory  mus- 
cles unquestionably  contribute  some  small  quota  to  the  total  increase  in  metab- 
olism. We  commend  to  the  attention  of  the  physician  the  importance  of  the 
pulse-rate  in  diabetes  and  particularly  the  value  of  changes  in  the  pulse-rate  in 
the  same  patient  during  the  progress  of  the  disease.  We  like'vvise  commend  to 
all  experimenters  the  practice  first  established  by  Prout^  of  reporting  the 
pulse-rate  with  the  chemical  data  of  each  experiment. 

Body  -Temperature. 

In  a  research  of  this  kind,  measurements  of  body-temperature  have  two 
purposes.  First,  to  learn  whether  the  temperature  measurements  are  within 
normal  limits  and,  second,  for  use  in  computing  the  heat  production.  The 
variations  in  body-temperature  necessitate  proper  corrections  for  heat  stored 
when  the  body-temperature  rises,  or  for  heat  given  off,  and  thus  not  produced, 
as  the  body-temperature  falls.  An  ideal  experiment,  therefore,  would  call  for 
continuous  measurements  of  body-temperature,  particularly  at  the  beginning 
and  end  of  each  experimental  period.  In  this  laboratory  and  in  the  laboratory 
of  Wesleyan  University,  Middletown,  Connecticut,  much  attention  has  been 
paid  in  the  last  ten  years  to  such  measurements.     To  obtain  the  most  accurate 

iProut,  Ann.  Philos.,  1813,  2,  p.  328. 


88 


METABOLISM   IN    SEVERE   DIABETES. 


calorimetric  measurements,  an  electrical  resistance  thermometer  which  can  be 
inserted  deep  in  the  rectum  has  been  used  for  measuring  rectal  temperatures, 
but  a  number  of  the  diabetic  subjects  found  this  somewhat  objectionable, 
although  in  no  sense  painful.  Accordingly,  in  many  instances  we  were  obliged 
to  content  ourselves  with  temperatures  taken  in  the  mouth  by  means  of  a 
mercurial  clinical  thermometer  of  good  grade.  With  a  number  of  subjects, 
however,  we  were  able  to  determine  the  rectal  temperature  by  the  electrical 
resistance  method.  In  general,  the  fluctuations  and  actual  temperature 
measurements  ranged  well  within  what  are  commonly  supposed  to  be  normal 
limits;  only  one  of  the  diabetic  subjects  showed  a  body-temperature  that 
could  be  considered  in  any  sense  above  normal,  and  even  normal  individuals 
have  indicated  equally  as  high  a  temperature  as  did  this  diabetic  subject. 
Table  110. — Body-temperature  of  diabetic  subjects. 


Subject. 

Sublingual.! 

Rectal. 2 

Maximum.' 

Minimum.' 

Maximum. 

Minimum. 

A 

B 

C    

op 

98.4    (36.90) 
98.0    (36.65) 

°F. 

97.2    (36.20) 
97.6    (36.45) 

°C. 

37.07 

37!  32 
38!  05 

"C. 
36.30 

36!  49 
37!  70 

36!  93 
36,56 
36.44 

E 

F 

G       

99.0    (37.20) 
98.95  (37.20) 

98.6    (36.65) 
97.95  (36.65) 

H 

I 

98.6    (37.00) 
98.65  (37.05) 
98.55  (36.95) 

97.6    (36.45) 
97.75  (36.55)< 

J 

98.25(36.80)             

K 

L 

M 

N 

U 

X 

37.14 

98.3    (36.85) 

97.90  (36.60) 

37.71 
37.11 

98.7    (37.05) 
98.6    (37.00) 
98.2    (36  80) 

97.02  (36.10) 
98.4    (36.90) 
97.1    (36.15) 

>  Records  taken  with  a  clinical  thermometer. 
2  Records  taken  with  an  electrical  resistance  thermometer. 
'Centigrade  equivalents  given  in  parentheses. 
<For  Case  I  there  was  also  97.3°  F.  (36.28°  C.)  on  Feb.  23,  1911, 
sitting  in  chair  after  the  experiment. 

To  give  an  indication  of  the  minimum  and  maximum  temperatures 
observed  with  the  diabetics,  we  have  collected  in  table  110  the  values  for  both 
the  sublingual  temperatures  taken  with  a  mercurial  thermometer  and  likewise 
the  rectal  temperatures  taken  with  the  electrical  resistance  thermometer.  An 
inspection  of  the  data  shows  that  the  sublingual  temperatures  are  practically 
those  ordinarily  experienced  with  normal  individuals  in  health.  The  rectal 
temperatures  are  almost  invariably  somewhat  higher  than  are  the  sublingual 
temperatures,  as  would  be  expected  from  the  well-known  fact  that  tempera- 
tures in  the  rectum  are  considerably  higher  than  those  in  the  mouth.  With 
one  subject.  Case  G,  the  temperature  was  somewhat  higher  than  normal, 
averaging  close  to  38°  C.  throughout  the  whole  experiment. 

Since  the  publication  of  our  first  report  on  metabolism  in  diabetes,  a 
research  has  been  concluded  in  this  laboratory,^  demonstrating  what  has 
hitherto  been  assumed,  namely,  that  fluctuations  in  temperature  taken  deep 


^Benedict  and  Slack,  A  comparative  study  of  temperature  fluctuations  in  different 
parts  of  the  human  body,  Carnegie  !lnstitution  of  Washington  Publication  No.  155, 1911. 


DISCUSSION   OF   RESULTS   AND   GENERAL   CONCLUSIONS.  89 

in  the  rectum  are  accompanied  by  similar  fluctuations  in  different  parts  of  the 
body.  For  purposes  of  computing  the  heat  production,  it  is  most  necessary 
to  know  if  an  alteration  in  temperature  of  0.1  degree  in  any  one  part  of  the 
body  shows  a  like  alteration  in  the  temperature  of  the  body  as  a  whole,  the 
absolute  temperatures  not  being  so  significant.  The  investigation  referred  to 
has  shown  that  when  the  rectal  temperature  falls  0.1  degree,  there  is  a  corre- 
sponding fall  in  all  other  parts  of  the  body;  hence  it  is  logical  to  assume  that  a 
change  of  temperature  measured  in  the  rectum  may  be  ascribed  to  that  of  the 
whole  body.  In  computing  the  heat  production,  therefore,  correction  can  be 
made  for  the  heat  lost  from  the  body  when  there  is  a  lowering  in  the  tempera- 
ture by  multiplying  the  specific  heat  of  the  body  by  its  weight  and  by  the 
loss  in  temperature  as  measured  in  the  rectum. 

The  importance,  therefore,  of  this  table  is  that  it  establishes  the  fact  that 
the  temperatures  of  diabetics  as  a  rule  range  well  within  what  are  commonly 
supposed  to  be  the  normal  limits.  We  wish,  however,  to  point  out  here  the 
difficulties  experienced  by  Benedict  and  Slack  in  securing  adequate  and  proper 
records  of  the  body-temperature  by  means  of  the  mercurial  thermometer  in  the 
mouth.  As  a  means  of  indicating  the  presence  or  absence  of  a  high  fever  this 
method  is  certainly  rational,  but  for  all  physiological  purposes  and  especially 
for  the  measurement  of  small  differences  in  temperature,  observations  taken  in 
the  mouth  are  wholly  unsatisfactory  and  no  reliance  should  be  placed  upon 
them.  On  the  other  hand,  rectal  temperatures  should  be  taken  deep  in  the 
rectum,  the  thermometer  being  inserted  at  least  5  cm.  if  the  true  internal 
temperature  of  the  body  is  to  be  recorded. 

BODY-WEIGHT. 

Perhaps  no  one  gross  observation  made  during  the  course  of  diabetes  melli- 
tus  is  of  greater  significance  and  causes  greater  alarm,  both  to  patient  and 
physician,  than  the  persistent  loss  in  body-weight.  On  the  other  hand,  slight 
changes  in  body-weight  which  may  accompany  dietetic  alterations  or  the  inges- 
tion of  sodium  bicarbonate  are  looked  upon  as  material  gains  and  of  diagnostic 
value,  and  are  thus  liable  to  be  misunderstood  by  the  patient.  To  interpret 
intelligently  these  changes  it  is  necessary  both  for  the  physician  and  for  the 
patient  to  realize  the  factors  affecting  the  body-weight  of  normal  as  well  as 
pathological  cases. 

Few  realize  that  the  normal  individual  is  continually  undergoing  changes 
in  body-weight  throughout  the  24  hours.  The  extent  and  rapidity  of  these 
fluctuations  may  best  be  shown  by  means  of  a  chart  obtained  from  observations 
made  every  hour  for  24  hours.  (See  fig.  1.)  The  subject  was  weighed  on  a 
sensitive  platform  balance;  the  total  weight  of  food  eaten  at  different  times 
was  recorded,  also  the  total  weight  of  drinking-water  when  it  was  taken,  and 
the  weight  of  urine  and  the  weight  of  feces  when  passed.  In  addition  to  being 
weighed  every  hour,  the  subject  was  weighed  immediately  before  and  after 
eating  or  drinking,  passing  urine,  or  defecating.  Two  series  of  observations 
were  made,  the  results  of  which  are  shown  in  curves  I  and  II.     Curve  I  gives 


90 


METABOLISM   IN    SEVERE   DIABETES. 


a  record  of  hourly  weighings  taken  when  the  subject  was  awake  the  whole  24 
hours;  curve  II  shows  the  results  of  hourly  weighings  made  during  the  waking 
hours,  also  a  record  of  the  total  loss  during  the  night  sleep. 

In  curve  I  it  can  be  seen  that  except  at  the  times  when  food  was  taken 
there  was  a  downward  tendency  of  the  curve  throughout  the  whole  24  hours. 
As  a  matter  of  fact,  the  general  angle  of  the  curve  with  the  base-line  is  essen- 
tially the  same  throughout  the  whole  day.  During  this  experiment  the  subject 
was  engaged  in  experimental  work  in  the  laboratory  which  necessitated  con- 
tinous  observation  during  the  24  hours,  and  hence  we  find  no  variations  in  the 
rapidity  of  the  combustion  of  materials  during  the  day  or  during  the  night. 
On  the  other  hand,  when  the  same  subject  spent  a  normal  amount  of  time  in 
bed  asleep,  the  course  of  the  curve  (curve  II)  is  somewhat  different.  During 
the  day  its  course  is  essentially  the  same  as  that  of  curve  I,  but  during  the  night 


1 


7-AM 


I2M  6-P;M  I2M 

Fig.  1. — Curves  showing  hourly  changes  in  body-weight  for  24  hours. 


6A:M 


Curve  I  shows  the  changes  in  body-weight  when  the  subject  was  awake  the  entire  24  hours. 
Curve  II  shows  the  changes  in  body-weight  when  the  subject  was  awake  from  7  a.m.  to   10  p.m.,  and  asleep 
from  10  p.m.  to  6  a.m. 

the  loss  is  much  less;  this  would  be  expected  from  the  fact  that  instead  of  being 
engaged  in  rather  active  muscular  work  about  the  laboratory,  the  subject  was 
in  bed  asleep.  Curve  I  furthermore  shows  that  the  long  night  work  was  rather 
severe  and  the  body-weight  was  noticeably  less  at  the  end  than  it  was  at  the 
beginning  of  the  experiment.  In  curve  II  the  body-weight  returned  to  essen- 
tially the  same  point  at  the  end  of  the  24  hours,  notwithstanchng  the  fluctua- 
tions due  to  the  ingestion  of  food  and  drink  and  the  loss  in  feces  and  urine. 
The  second  curve  shows  clearly,  therefore,  that  the  body-weight  varies  at 
different  times  of  the  day,  but  it  may  be  noticeably  different  on  different  days, 
easily  varying  1  or  2  pounds  in  the  course  of  a  single  day. 

It  is  obvious  that,  aside  from  the  loss  in  weight  due  to  the  passing  of  urine 
or  feces,  there  is  a  general  tendency  for  the  body  to  lose  weight  from  hour  to 


DISCUSSION    OF   RESULTS   AND   GENERAL    CONCLUSIONS. 


91 


hour.  This  is  due  to  a  loss  which  has  been  known  since  the  days  of  Sanctorius^ 
as  insensible  perspiration.  One  of  the  best  methods  of  observing  this  loss  in 
weight  in  the  form  of  insensible  perspiration  is  during  the  night.  If,  for 
example,  the  subject  is  weighed  just  before  going  to  bed  and  again  in  the  morn- 
ing immediately  on  rising  and  before  the  bladder  is  emptied,  the  loss  in  weight 
will  be  due  to  insensible  perspiration.  Two  such  experiments  were  made  with 
a  normal  man  weighing  approximately  85  kilos,  without  clothing  and  a  normal 
woman  weighing  65  kilos,  without  clothing.  The  results  are  shown  in  table 
HI,  which  gives  the  number  of  hours  spent  in  bed  and  the  loss  in  weight  in 
grams.  The  loss  in  weight  was  found  to  be  directly  proportional  to  the  restless- 
ness of  the  sleep,  as  on  a  hot,  uncomfortable  night  it  was  much  greater  than  on 
a  cold  night  when  the  person  slept  quietly  beneath  bedclothes,  instinctively 
moving  no  more  than  was  necessary.  On  the  average  the  man  lost  39  grams 
per  hour  and  the  woman  29  grams.  The  insensible  perspiration,  therefore,  was 
not  far  from  30  to  40  grams. 

Table  111. — Loss  in  body-weight  during  night. 


Man,  85  kilos. 

Woman,  65  kilos. 

Date. 

In  bed. 

Loss  in 
weight. 

Date. 

In  bed. 

Loss  in 
weight. 

1898. 
Oct     7.... 

Oct.    8 

Oct.    9.... 
Oct.  10.... 
Oct.  11.... 
Oct.  12.... 
Oct.  13.... 

hrs.   min. 
8      45 
8        0 

8  15 

9  0 
9        0 
8      15 
8        0 

gms. 
330 
360 
300 
310 
390 
360 
250 

1898. 
Oct   13.... 
Oct.  14.... 
Oct.  31.... 
Nov.  1.... 

hrs.  min. 

8  0 

9  45 
7      15 
9       0 

gms. 
170 
270 
230 
290 

Average  loss  per  hour:  Man,  39  grams:  woman,  29  grams. 

This  observation,  made  with  a  platform  balance,  of  the  loss  of  30  to  40 
grams  of  weight  by  insensible  perspiration  received  substantiation  from  the 
results  of  50  or  more  experiments  carried  out  in  the  Nutrition  Laboratory  by 
more  refined  and  exact  methods.  With  a  considerable  number  of  individual 
subjects  it  was  found  that  the  loss  due  to  insensible  perspiration,  during  wak- 
ing hours,  when  the  subject  was  sitting  stilP  inside  the  respiration  chamber, 
averaged  40  grams  per  hour.  In  certain  work  experiments  this  insensible 
perspiration  was  greatly  increased,  but  it  is  safe  to  say  that  a  normal  person, 
sitting  still  and  reading  quietly,  will  lose  in  weight  approximately  40  grams 
per  hour.  With  severe  muscular  work  the  loss  may  be  increased  tenfold,  or, 
indeed,  during  the  time  of  strenuous  muscular  exercise,  as  in  athletic  contests, 
even  a  hundredfold.  Although  the  amount  of  this  insensible  perspiration  can 
be  obtained  by  accurately  weighing  the  subject  on  scales,  the  character  of  the 
loss  can  be  determined  only  by  careful  respiration  experiments,  which  show 
that  carbon  dioxide  and  water-vapor  are  continually  being  given  off  from  the 

'Sanctorius,  De  medicina  statica  aphorismi,  Venice,  1614.  Translated  by  John 
Quincy,  M.  D.,  London,  1737. 

^  Benedict  and  Carpenter,  Carnegie  Institution  of  Washington  Publication  No.  126, 
1910.  p.  114. 


92  METABOLISM   IN    SEVERE   DIABETES. 

body  and  oxygen  consumed.  The  loss  in  insensible  perspiration  is,  then,  not 
simply  an  evaporation  of  water  from  the  body,  but  consists,  in  part  at  least,  of 
an  actual  loss  of  organized  body-tissue  that  has  been  oxidized  by  the  oxygen 
taken  into  the  lungs  and  given  off  both  as  carbon  dioxide  and  as  water  result- 
ing from  the  oxidation  of  organic  hydrogen. 

Referring  again  to  curves  I  and  II  in  fig.  1,  it  will  be  seen  that  the  increase 
in  weight  found  after  taking  food  was  due  simply  to  the  weight  of  the  food 
taken  into  the  intestinal  tract,  and  that  the  noticeable  losses  in  weight  follow- 
ing the  passage  of  urine  and  feces  were  due  to  the  loss  of  these  materials  from 
the  body.  In  discussing  changes  in  body-weight,  the  important  point  to  note 
is  whether  there  are  additions  to  or  losses  from  the  total  body-mass,  the  inci- 
dental fluctuations  due  to  the  taking  on  of  food  or  the  passage  of  urine  or  feces 
being  of  no  great  importance.  If,  then,  during  a  period  of  one  year,  the  body 
gradually  increases  in  weight  a  number  of  pounds  or  loses  a  number  of  pounds, 
it  is  clear  that  these  changes  in  weight  can  not  be  due  to  minor  fluctuations  in 
the  quantity  of  water  or  food  taken,  of  urine  passed,  or  of  feces  excreted. 

A  factor  which  should  be  taken  into  consideration  in  interpreting  changes 
in  body-weight  is  the  fluctuation  in  the  water-content  of  the  body.  Under 
certain  conditions  it  is  possible  for  the  body  to  retain  considerable  quantities  of 
water  and,  indeed,  to  be  deprived  of  considerable  amounts  of  water  that  would 
normally  be  retained.  Since  about  60  per  cent  of  the  body  is  water,  any 
change  of  water-content  may  result  in  material  gains  or  losses  in  body-weight. 
A  man  weighing,  for  example,  65  kilos,  may  have  an  absolute  water-content  of 
40  kilos.,  so  that  a  relatively  small  change  in  the  percentage  of  water  in  the 
body  may  produce  a  change  in  body-weight  of  1  kilo. 

It  was  observed  many  years  ago  by  Bischoff  and  Voit,^  in  a  series  of  experi- 
ments with  animals,  that  when  the  diet  was  in  large  part  carbohydrate  there 
was  a  tendency  for  the  body  to  retain  water  in  that  the  muscular  tissues  became 
more  moist.  By  means  of  the  respiration  calorimeter  at  Wesley  an  University, 
Middletown,  Connecticut,  an  interesting  experiment  was  made  on  a  man 
which  showed  conclusively  the  effect  of  the  constituents  of  a  diet  on  the  water- 
content  of  the  body.-  During  the  experiment,  which  lasted  6  days,  the  sub- 
ject was  confined  inside  of  a  respiration  chamber  and  spent  8  hours  of  the  day 
riding  a  stationary  bicycle  ergometer,  thereby  doing  a  considerable  amount  of 
muscular  work.  The  daily  routine  and  the  quantity  of  work  performed  were 
adjusted  so  that  they  would  be  the  same  on  all  days.  During  the  first  three 
days  the  subject  was  given  a  diet  containing  a  large  amount  of  carbohydrate, 
the  total  diet  being  nearly,  although  not  quite,  sufficient  to  supply  him  with 
energy  for  the  amount  of  work  he  was  to  do.  In  this  period,  which  was  pre- 
ceded by  a  preliminary  period  with  the  same  diet,  the  body  retained  its  weight 
for  a  number  of  days.  On  the  fourth  day  the  character  of  the  diet  was  materi- 
ally altered  by  decreasing  the  carbohydrate  and  increasing  the  fat.  Singularly 
enough,  although  the  actual  total  weight  of  food  ingested  was  somewhat  more 

'Bischoff  und  Voit,  Die  Gesetze  der  Ernahrung  des  Fleischfressers,  Leipsic,  1860. 
'Benedict  and  Milner,  U.  S.  Dept.  Agr.,  Office  Exp.  Stas.  Bui.  175,  1907,  p.  225. 


DISCUSSION    OF   RESULTS   AND    GENERAL   CONCLUSIONS. 


93 


than  on  the  first  three  days,  nevertheless  the  body  actually  lost  in  weight  950, 
839,  and  952  grams  on  the  first,  second,  and  third  days,  respectively,  thus 
showing  that  with  the  carbohydrate  diet  the  body  of  the  subject  had  a  ten- 
dency to  retain  a  much  larger  amount  of  water  than  with  the  fat  diet.  The 
results  of  this  experiment  are  presented  in  table  112. 

The  chemical  analyses  of  food,  feces,  and  excreta,  including  especially  the 
determination  of  carbon  dioxide  produced,  oxygen  consumed,  and  water  vapor- 
ized, give  the  data  for  the  exact  computation  of  the  kind  and  amount  of 
material  lost  from  the  bod3\  The  results  from  this  6-day  experiment  show 
that  the  quantities  of  the  food  had  been  so  adjusted  to  the  needs  of  the  bodj^ 
that  there  was  practically  no  draft  upon  body-material  or  storage  of  either  pro- 
tein, fat,  or  carbohydrates,  but  that  there  were  great  changes  in  the  amount  of 
water.  It  was  found  on  the  average  that  the  body  actually  stored  165  grams 
of  water  per  day  during  the  carbohydrate  period  and  actually  lost  on  the  aver- 

Table  112. — Changes  in  body-weight  due  to  diet. 
CARBOHYDRATE  DIET. 


Date  and 
diet. 


1904. 

Apr.  16 

16-17.. 
17-18.. 
18-19.. 


Food  and  drink. 


Solid 

matter. 


Water,  i  Total. 


gins. 

970 
966 
966 


3577  4547 
3553  4519 
3491        4457 


Body- 
weight. 


I  Gain  (+) 
I    or  loss 


ttZos. 
75.086 
75.443 
75.414 
75.269 


+357 
-  29 
-145 


FAT  DIET. 


Apr.  19-20. . 

750 

3108 

3859 

74.319 

20-21.. 

745 

4150 

4896 

73.480 

21-22.. 

747 

4152 

4899 

72.528 

-950 
-839 
-952 


grams. 

Average  gain  per  day,  carbohydrate  diet +61 

Average  loss  per  day,  fat  diet —914 

Water  stored  per  day,  carbohydrate  period +165 

Water  lost  per  day,  fat  period —906 

age  906  grams  of  water  per  day  during  the  fat  period.  This  loss  during  the  fat 
l^eriod  corresponds  almost  exactly  ■with  the  loss  in  body-weight,  and  shows 
that  the  loss  is  due  to  water.  Similar  experiments  have  shown  that  the  reverse 
is  true,  i.  e.,  when  the  previous  diet  contained  a  preponderance  of  fat  and  the 
change  was  suddenly  made  to  a  carbohj'drate  diet,  there  was  a  marked  increase 
in  weight.  Obviously,  there  would  be  a  limit  to  such  retention  of  water,  since 
the  body  would  not  continue  indefinitely  to  accumulate  water  at  the  rate  of 
500  or  600  grams  a  day,  as  it  would  soon  become  ''waterlogged"  under  these 
conditions.  There  is,  however,  something  in  the  character  of  a  rich  carbo- 
hydrate diet  which  seems  to  demand  a  larger  proportion  of  water,  and  this 
demand  is  provided  for  by  a  storage  of  water  in  the  body-tissue;  when  the 
carbohydrate  diet  is  changed  to  a  fat  diet,  this  water  is  freely  excreted.  The 
restriction  of  carbohydrate  and  the  increase  of  fat  which  are  prescribed  when. 
diabetic  patients  are  first  started  upon  dietetic  treatment  duplicate  the  above 


94 


METABOLISM   IN    SEVERE   DIABETES. 


experiment  and  the  loss  of  weight  which  such  patients  usually  undergo  at  once 
is  thus  in  part  explained.  Conversely,  a  gain  in  weight  almost  universally 
accompanies  the  oatmeal  cure. 

That  other  conditions  also  play  an  important  role  in  the  storage  of  water 
in  the  body  has  been  shown  in  our  extensive  experience  with  diabetics.  It  has 
been  frequently  found  that  when  diabetics  are  on  a  strict  diet  and  are  given 
relatively  large  amounts  of  sodium  bicarbonate  to  counteract  the  ever-present 
tendency  to  acidosis,  there  may  be  a  considerable  retention  of  water  and  con- 
sequent increase  in  body-weight  inside  of  a  few  days.  An  abstract  of  the 
results  with  one  of  the  cases  (Case  A)  is  given  in  table  113.  The  records  of 
the  body-weights  were  made  in  the  early  morning  before  food  was  taken. 
Beginning  November  6,  20  grams  of  sodium  bicarbonate  were  given  daily,  and 
the  results  show  that  while  the  body-weight,  on  the  morning  of  November  6, 
was  49.3  kilos.,  on  the  morning  of  November  11  it  had  increased  to  53.3  kilos., 
or  a  gain  of  4  kilos.  Since  at  this  time  the  subject  was  living  on  a  very 
restricted  diet,  with  barely  enough  energy  in  the  diet  for  daily  maintenance,  it 
can  be  seen  that  this  increase  must  have  been  due  not  to  the  retention  of  organ- 
ized body-material,  either  protein  or  fat,  but  simply  to  water.  If  the  dietetic 
conditions  had  been  reversed,  an  equally  rapid  loss  in  weight  would  have  been 
expected,  corresponding  to  the  amount  of  water  lost. 

Table  113. — Gain  in  weight  ofadiabetic  with  administration  of  sodium  bicarbonate  * 


Date. 

Sodium 
bicar- 
bonate. 

Body- 
weight. 

Date. 

Sodium 
bicar- 
bonate. 

Body- 
weight. 

Nov.  2 

3 

4 

5 

6 

gms. 
0 
0 

s 

20 

kilos.      ' 

48  1 

48.6 

49.0 

48.6 

49.3 

Nov.    7... 
8... 
9... 
10... 
11... 

gms. 
20 
20 
20 
20 
20 

kilos. 

50  7 

51  5 

52  4 
53.3 
53.3 

*The  proportions  of  protein,  carbohydrate,  and  fat,  as  well  as  total  calories,  were  nearly  constant  throughout. 

While  a  knowledge  of  the  fluctuations  in  body-weight  due  to  the  retention 
or  loss  of  water  plays  an  important  role  in  gaining  a  correct  understanding  of 
the  significance  of  changes  in  body-weight,  we  need  pay  particular  attention 
only  to  drafts  upon  organized  body-material.  Of  the  four  remaining  constit- 
uents of  the  body- — the  protein,  fat,  carbohydrate,  and  the  mineral  matter — 
the  largest  addition  or  depletion  can  be  made  in  the  case  of  fat.  Additions 
to  the  protein  content  of  the  body  are  not  so  easily  made  as  are  additions  to 
the  fat.  Experiments  in  the  laboratory  of  Professor  von  Noorden^  have  shown, 
however,  that  considerable  quantities  of  nitrogenous  material  can  be  stored  in 
the  body,  but  how  this  is  stored  and  in  what  form  is  by  no  means  certain.  It  is, 
however,  reasonably  certain  that  the  protein  is  not  stored  in  the  form  of  active 
protoplasmic  tissue  which  necessitates  an  active  metabolism.  After  the  body 
has  been  subjected  to  a  fast  it  seems  to  have  an  especial  ability  to  restore  the 
loss  of  nitrogenous  material  and  even  take  on  a  greater  amount.     While  under 

■  'See  Miiller,  Zentralblatt  f.  die  ges.  Path.  u.  Pharm.  des  Stoffwechsels.  1911,  6,  p.  617. 


DISCUSSION    OF  RESULTS   AND   GENERAL   CONCLUSIONS.  95 

special  experimental  conditions  it  is  possible  for  us  to  add  to  or  take  from  the 
store  of  nitrogen  in  the  body  to  the  extent  of  several  hundred  grams,  never- 
theless this  is  rarely  accomplished.  Consequently,  in  studying  fluctuations  of 
body-weight  ordinarily  occurring  outside  of  those  attendant  upon  wasting  dis- 
eases, we  do  not  need  to  consider  any  alterations  in  the  storage  of  body  nitrogen. 

One  of  the  most  important  compounds  in  the  human  body  is  the  relatively 
small  quantity  of  carbohydrate  material,  chiefly  in  the  form  of  glycogen  in  the 
Uver  and  muscles.  While  it  is  believed  that  there  may  be,  relatively  speaking, 
a  large  draft  upon  this  storage  of  body-glycogen,  which  has  been  estimated  by 
some  writers  to  be  not  more  than  400  grams,  the  total  fluctuation  one  way  or 
the  other  is  not  of  suflficient  moment  to  play  any  part  in  considering  the  major 
changes  in  body-weight.  It  is  possible,  indeed  probable,  that  varying  amounts 
of  glycogen  may  indirectly  control  or  influence  the  presence  of  varying  amounts 
of  water,  but  glycogen  per  se  can  not  be  materially  added  to  the  body  or  taken 
from  the  body,  since  the  total  storage  is  small — probably  not  far  from  400 
grams.  The  remaining  compound  of  the  body,  i.  e.,  fat,  can,  however,  be 
enormously  added  to  or  taken  from.  It  is  with  changes  in  the  storage  or  loss 
of  fat  that  we  have  chiefly  to  do  when  discussing  the  question  of  the  gains  and 
losses  in  body-weight,  particularly  losses  that  are  the  result  of  a  progressive 
change  covering  some  weeks  or  months. 

It  has  already  been  pointed  out  how  by  certain  abnormal  conditions  we 
can  produce  rapid  fluctuations  in  the  water-content  of  the  body,  but  it  is  prac- 
tically impossible  to  secure  any  rapid  change  in  the  amount  of  fat  stored  or  lost 
by  the  body.  Even  fasting  for  a  day  does  not  lead  to  any  appreciable  draft 
upon  the  storage  of  fat.  It  has  been  proved  that  in  a  normal  healthy  indi- 
vidual undergoing  a  complete  fast  for  24  hours,  the  glycogen  may  be  depleted 
to  the  extent  of  possibly  one-half  of  its  original  value.  Then  after  this  deple- 
tion of  glycogen  has  taken  place,  the  fat  is  drawn  upon,  and  after  the  third  day 
the  draft  is  chiefly  upon  the  fat-content  of  the  body,  with  a  relatively  small  but 
constant  depletion  of  the  glycogen  and  protein;  thus  it  is  seen  that  any  changes 
in  weight  having  to  do  with  1  or  2  pounds  inside  of  24  hours  can  not  in  any 
way  be  considered  as  changes  in  the  fat-content  of  the  body. 

To  study  the  character  of  these  changes,  respiration  experiments  are  essen- 
tial, in  which  the  carbon-dioxide  production  is  determined  as  well  as  the  oxygen 
intake  and,  if  possible,  the  vaporization  of  water.  If  we  Avere  to  collect  all  of 
the  products  of  expiration  from  the  body,  namely,  the  carbon  dioxide  and 
water-vapor,  we  would  not  even  then  have  an  equivalent  of  the  material  lost 
from  the  body,  for  of  the  carbon  dioxide  and  that  portion  of  the  water  which  is 
formed  by  the  oxidation  of  organic  hydrogen,  a  not  inconsiderable  amount  is 
due  to  the  weight  of  the  oxygen  absorbed  from  the  air.  For  instance,  assuming 
that  a  man  at  rest  in  24  hours  produces  700  grams  of  carbon  dioxide  and  gives 
off  900  grams  of  water  by  sensible  and  insensible  perspiration,  this  total  weight 
of  1,600  grams  does  not  by  any  means  represent  the  loss  from  the  body,  since 
of  this  amount  at  least  700  grams  is  due  to  the  oxygen  absorbed  out  of  the  air, 
and  the  actual  loss  from  the  body  would  therefore  be  approximately  900  grams 
of  water  and  organic  material. 


96 


METABOLISM   IN    SEVERE   DIABETES. 


Here  again  we  find  the  ever-occurring  changes  in  water-content  com- 
pletely masking  all  information  with  regard  to  the  loss  of  organized  body-tissue. 
The  water  given  off  from  the  body  is  from  two  sources,  first,  the  preformed 
water  existing  as  such  in  the  tissues,  and,  second,  the  water  resulting  from  the 
oxidation  or  burning  of  organized  body-material.  The  respiration  calorimeter 
with  its  accessory  appliances  shows  us  the  method  by  which  the  water  leaves 
the  body,  but  it  does  not  tell  us  whether  the  water  from  these  two  sources  has 
any  selective  method  of  discharge;  thus,  all  the  water  formed  from  the  combus- 
tion of  organic  tissue  is  not  excreted  through  the  lungs  and  skin,  nor  is  the 
water  drunk  all  excreted  through  the  kidneys.  The  data  for  the  losses  in 
gross  weight  cease  to  be  of  any  service  to  us,  therefore,  in  telling  us  what  pro- 
portion of  the  daily  loss  is  due  to  the  oxidation  of  organized  tissue. 

As  a  result  of  a  large  number  of  calorimetric  experiments  on  men,  both  fast- 
ing and  with  food,  it  can  be  shown  that  the  average  man  at  rest  without  food 
may  oxidize  per  day  about  75  grams  of  protein,  25  grams  of  glycogen,  and  200 
grams  of  fat,  a  total  of  300  grams  of  water-free  organized  body-tissue.  It  can 
be  readily  seen,  therefore,  that  with  subjects  at  rest  large  changes  in  weight 
must  be  due  not  to  the  oxidation  of  organic  matter,  Avhich  amounts  to  only  300 


Table  114. — Loss  in  body-weight  after  severe  muscular  exercise. 


Subject. 


Duration 
of  work. 


Football  player , 

Marathon  runner 

College  8-oared  boat  crew 


hrs.  min. 
1    10 
3      0 
0    22 


Loss  in 
weight. 


lbs. 
14.0 
8.5 
5.5 


kilos. 
6.4 
3.9 
2.5 


grams  per  day,  but  to  large  excretions  of  water.  With  increased  muscular 
activity  we  have  both  increased  destruction  of  organized  tissue  and  likewise 
very  large  increases  in  the  amount  of  water  lost  from  the  body.  This  is  well 
shown  by  the  records  of  losses  in  body-weight  due  to  the  excessive  exercise  of 
athletes,  and  while  the  observations  lack  that  finality  in  conclusions  that  experi- 
ments in  the  calorimeter  have,  yet  they  are  of  great  interest.  The  strenuous 
exercise  incidental  to  eight-oared  boat  racing  and  to  football  games,  particu- 
larly in  the  early  fall,  when  the  subjects  are  not  perfectly  trained  and  when  the 
weather  is  liable  to  be  hot,  has  frequently  been  made  the  subject  of  more  or  less 
observation.  Thanks  to  the  kindness  of  Prof.  William  G.  Anderson,  of  the 
Yale  University  gymnasium,  we  are  able  to  present  authoritative  figures  on 
this  subject.  A  number  of  years  ago  a  well-known  football  player  at  Yale  was 
weighed  before  and  after  a  contest  which  lasted  in  all  about  an  hour  of  actual 
playing.  During  the  period  this  man,  whose  original  body-weight  was  191 
pounds,  actually  lost  14  pounds.  This  observation,  together  with  some  others 
likewise  furnished  by  Professor  Anderson,  are  given  in  table  114.  As  pre- 
viously stated,  a  man  sitting  quietly  loses  weight  as  the  result  of  insensible 
perspiration  approximately  40  grams  per  hour.  The  football  player  lost  6,000 
grams,  or  150  times  as  much. 


DISCUSSION    OF   RESULTS   AND    GENERAL   CONCLUSIONS.  97 

It  is  impracticable  inside  the  narrow  confines  of  a  respiration  calorimeter 
to  study  the  metabolism  of  Marathon  runners  or  a  college  eight-oared  boat 
crew,  but  a  bicycle  rider,  riding  to  the  limit  of  human  endurance,  has  been 
studied. 1  If  we  use  the  figures  for  carbon-dioxide  production  and  oxygen  con- 
sumption determined  on  this  professional  rider,  we  shall  be  able  to  compute  the 
probable  loss  in  weight  from  the  body  of  the  football  player  which  was  due  to 
the  oxidation  of  organic  material;  by  deducting  this  loss  from  the  total  weight, 
we  can  find  the  loss  due  to  the  insensible  and  sensible  perspiration.  The  bicy- 
clist produced  200  grams  of  carbon  dioxide  per  hour  and  absorbed  121  grams  of 
oxygen.  Since  practically  all  of  the  oxygen  absorbed  was  immediately  given 
off  in  combustion  products,  we  may  infer  that  of  the  total  loss  in  weight  from 
the  body  the  carbon  sufficient  to  produce  200  grams  of  carbon  dioxide  repre- 
sents approximately  the  amount  of  organic  material  lost  from  the  man's  body 
during  one  hour  of  severe  muscular  work,  although  there  should  also  be  a  small 
allowance  for  hydrogen.  It  is  safe  to  say,  therefore,  that  during  an  hour  of 
exceedingly  hard  muscular  work,  such  as  this  strenuous  football  player  indulged 
in,  there  would  be  burned  in  the  body  not  far  from  100  grams  of  dry  organic 
material.  This  is  approximately  a  quarter  of  a  pound,  leaving  a  total  of  13.75 
pounds  of  lost  weight  due  to  water.  However,  eating  and  drinking  caused  the 
body-weight  of  the  subject  to  return  to  normal  inside  of  48  hours. 

This  illustration  not  only  serves  admirably  to  show  the  enormous  fluctua- 
tions that  can  take  place  in  the  body  in  a  very  short  time,  but  also  gives  us  a 
hint  as  to  the  possible  cause  of  sudden  changes  in  body-weight  such  as  may  be 
experienced  inside  of  24  or  48  hours,  namely,  that  these  changes  in  body-weight 
must  of  necessity  be  due  to  changes  in  the  water-content  and  not  to  changes  in 
the  organic  constituents  of  the  body.  In  mild  diabetes  the  initial  loss  in  body- 
weight  may  therefore  well  be  due  in  large  part  to  loss  of  water,  and  although 
there  may  be  a  rapid  fall  in  body-weight,  sufficient  to  alarm  both  patient  and 
physician,  it  need  not  necessarily  represent  the  loss  of  organized  tissue;  it  may 
simply  be  due  to  the  restriction  of  carbohydrate  during  the  process  of  getting 
the  patient  sugar-free.  During  the  initial  course  of  the  disease,  therefore, 
changes  in  body-weight  are  liable  to  be  peculiarly  deceptive,  both  qualitatively 
and  quantitatively,  since  an  apparent  large  loss  in  body-weight  may  be  due 
exclusively  to  changes  in  water-content,  with  material  drafts  upon  the  organ- 
ized tissues.  After  this  prefiminary  period  with  marked  loss  in  body-weight 
has  passed,  it  is  probable  that  the  loss  is  then  due  to  tissue  disintegration. 

While  it  is  true  that  sudden  initial  changes  in  body-weight  may  reasonably 
be  ascribed  to  fluctuations  in  the  water-content  of  the  body,  it  nevertheless 
remains  a  fact  that  an  inevitable  consequence  of  diabetes,  especially  when 
severe,  is  a  persistent  and  considerable  loss  in  weight.  Although  it  is  difficult 
to  obtain  accurate  data  from  patients  with  regard  to  their  greatest  body- 
weight  in  health,  particularly  Avithout  clothes,  we  have  attempted  in  all  these 
cases  to  secure  information  with  regard  to  this  important  factor.  These 
weights  are  given  in  table  115,  together  with  the  minimum  weight  observed  by 

'Benedict  and  Carpenter,  U.  S.  Dept.  Agr.,  Office  Exp.  Stas.  Bui.  208, 1909,  p.  29. 


98 


METABOLISM   IN   SEVERE   DIABETES. 


US  or  at  death.  From  these  the  loss  in  body-weight  has  been  computed,  as 
well  as  the  percentage  loss.  It  is  seen  that  in  these  cases  the  loss  in  body- 
weight  varied  from  5.4  to  48.3  per  cent  of  the  initial  highest  body-weight,  with 
an  average  loss  of  22.7  per  cent.  It  is  thus  clear  that  a  large  percentage  loss 
in  body-weight  is  almost  regularly  observed  in  severe  diabetes. 

On  some  200  cases  taken  from  several  hundred  in  the  practice  of  one  of  us 
(E.  P.  J.)  we  have  likewise  computed  the  percentage  loss  in  body-weight, 
using  the  highest  and  minimum  body-weights  observed.  These  are  given  in 
table  116.  It  so  happens  that  the  maximum  percentage  loss  observed  in  these 
200  cases  (that  of  Case  No,  3,  an  excessively  fat  individual)  was  but  slightly 
greater  than  that  observed  in  our  Case  R,  who  had  an  initial  body-weight 
essentially  one-half  that  of  Case  No.  3.  We  have  also  computed  the  loss  in 
weight  experienced  by  these  patients  before  being  seen  by  E.  P.  J.  as  an  index 
of  the  degree  of  emaciation  which  patients  usually  reach  before  coming  under 
special  treatment  for  diabetes.     It  should  be  borne  in  mind  that  these  losses  in 

Table  115. — Comparison  of  body-weights  of  subjects  in  health  and  disease. 


Greatest 
body- 
weight 

in  health. 

Minimum 

Ix)ss  in 

Per  cent 
loss  of 

Greatest 
body- 
weight 

in  health. 

Minimum 

Loss  in 

Per  cent 
loss  of 

Subject. 

weight 

body- 

original 

Subject. 

weight 

body- 

original 

observed. 

weight. 

best 
weight. 

observed. 

weight. 

best 
weight. 

kilos. 

kilos. 

kilos. 

p.ct. 

kilos. 

kilos. 

kilos. 

p.  ct. 

Case  A 

68.0 

46.1 

21.9 

32.2 

CaseO 

60.8 

49.2 

11.6 

19.1 

B 

50.7 

37.5 

13.2 

26.0 

P 

49.9 

38.4 

11.5 

23.0 

C 

73.5 

54.9 

18.6 

25.3 

Q 

54.0 

51.1 

2,9 

5.4 

D 

57.3 

45.9 

11.4 

19.9 

R 

66.7 

34.5 

32  2 

48.3 

F 

80.5 

54.5 

26.0 

32.3 

S 

71.1 

57.5 

13.6 

19.1 

G 

73.6 

53.1 

20.5 

27.9 

T 

71.2 

50.6 

20.6 

28.9 

H 

57.7 

49.2 

8.5 

14.7 

U 

53.1 

35.8 

17.3 

32.6 

I 

56.8 

39.3 

17.5 

30.8 

V 

63.5 

58.3 

5.2 

8.2 

J 

59.1 

61  5 

7.6 

12.9 

W 

63.5 

51.7 

11.8 

18.6 

K 

73.2 

55.6 

17.6 

24.0 

X 

90.7 

62.3 

28.4 

31.3 

L 

M 

79.1 
86.4 

62.2 
80.6 

16.9 
5.8 

21.4 
6.7 

Average . . . 

22.7 

N 

34.5 

29.6 

4.9 

14.2 

weight  of  diabetic  patients  are  not  necessarily  the  result  of  a  sudden  change  in 
1  or  2  weeks,  but  usually  extend  over  a  period  of  several  months;  the  only 
inference  that  can  be  drawn  is  that  patients  undergoing  such  losses  in  body- 
weight  are  prone  to  delay  dietetic  treatment  too  long. 

The  gains  in  weight  of  diabetics  noted  on  the  administration  of  sodium 
bicarbonate  or  following  a  change  in  the  diet  with  the  ingestion  of  large  amounts 
of  carbohydrate  in  the  form  of  oatmeal  raay  be  and  probably  are  due  wholly  to 
the  variations  in  composition  of  the  water-content  of  the  body;  hence  such 
gains  are  not  to  be  considered  as  additions  to  organized  body-tissue.  The 
tendency  of  optimistic  patients  to  consider  the  gain  in  weight  of  a  pound  or 
more  as  an  advantageous  sign  must,  in  certain  instances  at  least,  be  dispelled 
by  the  attending  physician,  who  should  explain  that  the  change  in  body-weight 
is  probably  due  to  a  change  in  the  water-content  of  the  body,  and  in  some  cases 
can  demonstrate  this  by  calling  attention  to  the  appearance  of  edema.  With 
the  diabetic  cases,  therefore,  we  have  practically  two  fundamentally  different 
alterations  in  body-weight  to  be  considered :  first,  an  initial  rapid  loss  in  weight 


DISCUSSION    OF   RESULTS   AND    GENERAL    CONCLUSIONS. 


Table  116. — Losses  in  body-weight  by  diabetics. 

[Weights  without  clothing.] 


Loss  in  weight  previous 

(a) 

(b) 

Weight  at 

our  first 

observation. 

to  observation. 

Minimum 

weight 
observed. 

Maximum  loss  in  weight. 

Case  No. 

Greatest 
weight. 

(c) 
Amount 

Per  cent 

Amount 

Per  cent 

(a-6). 

ic-^a). 

(a-e). 

(f-i-a). 

kilos. 

kilos. 

kilos. 

kilos. 

kilos. 

13 

110.3 

62.3 

48.0 

43.5 

50.5 

53.8 

48,8 

>5 

113.9 

111.2 

2.7 

2.4 

98.5 

15.4 

13.5 

17 

64.0 

51  1 

12  9 

20.2 

49.1 

14.9 

23.3 

8 

79.9 

70.8 

9.1 

11.4 

63.8 

16.1 

20.2 

no 

86.7 

68  6 

18.1 

20.9 

61.8 

24.9 

28^7 

>12 

64.0 

47.8 

16.2 

25.3 

45.4 

18.6 

29.1 

U3 

91.3 

79.5 

11  8 

12.9 

76.1 

15.2 

16  6 

114 

86.7 

69.0 

17.7 

20.4 

55.4 

31.3 

36  1 

"15 

61.8 

39.1 

22  7 

36.7 

'16 

98.5 

87.0 

n.5 

11.7 

86!3 

i2!2 

i2'4 

117 

71.8 

1          59.5 

12.3 

17.1 

59.5 

12.3 

17  1 

IS 

73.1 

57.2 

15.9 

21.8 

57.2 

15.9 

21  8 

119 

95.8 

80  0 

15.8 

16.5 

73.6 

22.2 

23  2 

21 

63.1 

50.6 

12.5 

19.8 

50.6 

12.5 

19.8 

25 

63.1 

45  3 

17.8 

28.2 

45.3 

17.8 

28  2 

26 

109.4 

99.9 

9.5 

8.7 

99.9 

9.5 

8.7 

128 

39.7 

34.2 

5.5 

13.9 

31.8 

7.9 

19.9 

131 

30.4 

26.8 

3.6 

11.8 

132 

82.2 

56.7 

25  5 

31.0 

33 

95.8 

94.9 

0.9 

0.9 

S2!6 

n.s 

liA 

34 

65.5 

65.5 

0 

0 

61.8 

3  7 

5.6 

136 

93.5 

83.8 

9.7 

10.4 

78.9 

14  6 

15.6 

37 

82.2 

67.6 

14.6 

17.8 

67.6 

14.6 

17.8 

138 

49.5 

45.0 

4.5 

9.1 

45.0 

4.5 

9  1 

139 

65.9 

59  7 

6.2 

9.4 

57.7 

8.2 

12.4 

140 

64.9 

55.4 

9.5 

14.6 

38  9 

26.0 

40.1 

141 

103.5 

75.4 

28  1 

27.2 

75.4 

28.1 

27  1 

142 

84.9 

68.1 

16  8 

19.8 

61.8 

23.1 

27.2 

144 

64.9 

56.8 

8.1 

12.5 

49.1 

15.8 

24.3 

145 

40.6 

34.5 

6  1 

15.0 

34.5 

6.1 

15.0 

46 

108.0 

79.9 

28.1 

26.0 

79.9 

28.1 

26.0 

148 

109.4 

74.7 

34.7 

31.7 

72.2 

37,2 

34  0 

49 

94.9 

82.4 

12.5 

13.2 

82.4 

12,5 

13.2 

151 

88.5 

65.7 

22.8 

25.8 

60.9 

27,6 

31.2 

152 

66.3 

50.1 

16.2 

24.4 

49,5 

16,8 

25.3 

154 

86.7 

49.8 

36.9 

42.6 

48.6 

38.1 

43,9 

155 

55  0 

52.7 

2.3 

4.2 

52.7 

2.3 

4,2 

156 

79.9 

61.7 

18.2 

22.8 

61.7 

18.2 

22  8 

157 

68.6 

56.6 

12.0 

17.5 

55.9 

12.7 

18,5 

59 

68.6 

59.3 

9.3 

13.6 

55.9 

12.7 

18.5 

162 

63.6 

46.3 

17  3 

27.2 

46.3 

17.3 

27.2 

164 

68.6 

48.6 

20.0 

29.2 

42.3 

26.3 

38  3 

65 

59.5 

58.3 

12 

2  0 

58.5 

1.0 

1.7 

166 

112.1 

89.9 

22.2 

19.8 

87.0 

25.1 

22.4 

70 

118.5 

107.8 

10.7 

9.0 

103.0 

15.5 

13.1 

71 

80.8 

78.0 

2.8 

3.5 

78.0 

2,8 

3.5 

172 

58.6 

55  2 

3  4 

5.8 

50.0 

8.6 

14.7 

173 

94.9 

77.8 

17.1 

18.0 

73  1 

21  8 

23.0 

75 

73.1 

58.6 

14.5 

19.8 

58.6 

14.5 

19,8 

76 

68.6 

55.3 

13.3 

19.4 

54.5 

14.1 

20,6 

77 

03.1 

44.6 

18.5 

29.3 

42.7 

20.4 

32  3 

78 

59.5 

55.5 

4  0 

6.7 

53.5 

6  0 

10  1 

179 

77.6 

60.4 

17.2 

22.2 

53  1 

24  5 

31,6 

■81 

75.8 

60.8 

15.0 

19  8 

60.8 

15.0 

19  8 

182 

58.4 

49.3 

9.1 

15.6 

49.3 

9.1 

15,6 

83 

62.2 

54.1 

8.1 

13  0 

54.1 

8.1 

13  0 

84 

107.1 

79.5 

27.6 

25.8 

73.2 

33.9 

31,7 

185 

93.5 

56.8 

36  7 

39  3 

56.8 

36.7 

39  3 

89 

97  2 

77.6 

19  6 

20  2 

73.1 

24  1 

24.8 

191 

64.0 

5!   1 

12.9 

20.2 

44.1 

19.9 

31.1 

92 

95.8 

82.8 

13.0 

13  6 

78.2 

17  6 

18.4 

93 

79.9 

64.8 

15.1 

18.9 

62  9 

17.0 

21.3 

194 

64.0 

48  7 

15.3 

23  9 

47.1 

16,9 

26.4 

97 

93.5 

75.8 

17.7 

18.9 

72,2 

21.3 

22.8 

95 

77.6 

67.5 

10.1 

13.0 

65  4 

12.2 

15.7 

100 

70.8 

63.6 

7.2 

10.2 

63  6 

7.2 

10.2 

1101 

75.4 

55.8 

19.6 

26.0 

55,8 

19,6 

26.0 

102 

79.9 

71.9 

8.0 

10.0 

66.8 

13.1 

16,4 

103 

104.9 

95.3 

9.6 

9.2 

75  4 

29.5 

28,1 

■105 

43.6 

41.5 

2  1 

4.8 

41.5 

2.1 

4,8 

107 

70.8 

44.5 

26.3 

37.1 

44.5 

26.3 

37  1 

1108 

61.8 

61  8 

0 

0 

57.2 

4.6 

7  4 

iDead. 


100 


METABOLISM    IN    SEVERE    DIABETES. 


Table  116. — Losses  in  body-weight  by  diabetics — Continued. 


(fl) 

(ft) 

Weight  at 

our  first 

observation. 

Loss  in  weight  previous 
to  observation. 

(e) 
Minimum 

weight 
observed. 

Maximum  loss  in  weight. 

Case  No. 

Greatest 
weight. 

i         (0 
i     Amount 

Per  cent 

(/) 
Amount 

Per  cent 

(a-b). 

ic-i-a). 

(a-e). 

(/-a). 

kilos. 

kilos. 

] 

kilos. 

kilos. 

kilos. 

"109 

.39.7 

39.1 

'            0.6 

1.5 

39,1 

0.6 

1.5 

111 

116.2 

108.8 

!           7.4 

6,4 

107,7 

8.5 

7.3 

•112 

104.4 

82.6 

j          21.8 

20,9 

79,6 

24.8 

23.8 

113 

82.2 

82.4 

+  0.2 

+  0,2 

82.2 

0 

0 

114 

65.9 

56.1 

9.8 

14,9 

56.1 

9.8 

14.9 

»119 

32.0 

31.0 

1.0 

3  1 

31  0 

1.0 

3.1 

120 

100.3 

85.6 

14.7 

14,7 

79.7 

20.6 

20.5 

"121 

66  3 

39.2 

27.1 

40.9 

38.4 

27.9 

42.1 

122 

86.7 

77.1 

9.6 

11.1 

74.1 

12.6 

14.5 

124 

88.5 

73.4 

15.1 

17.1 

73.4 

15.1 

17.1 

126 

82.2 

72.7 

9.5 

11.6 

72.5 

9.7 

11,8 

"129 

15.2 

13.4 

1.8 

11.8 

12  9 

2.3 

15  1 

130 

70,4 

55.1 

15.3 

21.7 

.55.1 

15.3 

21,7 

131 

102.6 

92.4 

10.2 

9.9 

80.4 

22.2 

21,6 

"132 

79.0 

61.8 

17.2 

21.8 

53.6 

25.4 

32,2 

"133 

90.3 

69.8 

20,5 

22.7 

65.9 

24.4 

27,0 

"134 

81.7 

58.6 

23,1 

28.3 

50.2 

31.5 

38,6 

"135 

58.6 

54.8 

3,8 

6.5 

33.1 

25.5 

43,5 

"137 

67.2 

51,0 

16,2 

24.1 

50.8 

16.4 

24,4 

"138 

61.8 

50.9 

10,9 

17.6 

50.9 

10  9 

17  6 

"139 

58.6 

52.2 

6,4 

10,9 

47.7 

10.9 

18,6 

"140 

77.6 

57.4 

20,2 

26,0 

574 

20.2 

26,0 

141 

102.6 

82.0 

20,6 

20,1 

81.7 

20.9 

20,4 

143 

62.7 

63.5 

+  0,8 

+  1,3 

57.2 

5.5 

8,8 

"145 

76.7 

63.8 

12,9 

16,8 

54  1 

22.6 

29,5 

"146 

60.4 

49.8 

10,6 

17,6 

49.8 

10.6 

17,6 

"147 

79.9 

65.5 

14.4 

18.0 

61  0 

18.9 

23,7 

149 

53.1 

53.4 

+  0.3 

+  0.6 

53.4 

+  0.3 

+  0,6 

317 

90.7 

64.5 

26.2 

28  9 

62.3 

28.4 

31,3 

"320 

63.5 

58.3 

5.2 

8  2 

58.3 

5.2 

8,2 

321 

102.6 

88.2 

14,4 

14.0 

86.7 

15.9 

15.5 

"324 

64.0 

38.4 

25,6 

40.0 

38.4 

25.6 

40  0 

'325 

25  2 

20.3 

4,9 

19.4 

20.2 

5.0 

19.8 

326 

97.1 

78.7 

18,4 

19.0 

78.7 

18.4 

19.0 

327 

109.4 

90.7 

18,7 

17.1 

90.7 

18.7 

17.1 

"328 

92.2 

78.5 

13.7 

14,9 

68.8 

23.4 

25,4 

329 

102.6 

91.5 

U.l 

10,8 

85.1 

17.5 

17  1 

330 

54.1 

47.2 

6,9 

12,8 

47.2 

6.9 

12,8 

331 

87.2 

87.8 

+  0.6 

+  0,7 

69.0 

18.2 

20  9 

"332 

53.1 

39  7 

13,4 

25.2 

35.8 

17.3 

32  6 

333 

63.5 

61.1 

2,4 

3.8 

51.7 

11.8 

18,6 

337 

112.6 

82.2 

30,4 

27.0 

82.2 

30.4 

27.0 

339 

69.5 

59.3 

10,2 

14.7 

56  3 

13.2 

19.0 

"340 

76.7 

63.8 

12.9 

16.8 

63.8 

12.9 

16.8 

341 

64.0 

59.8 

4.2 

6.6 

59  6 

4  4 

6  9 

343 

99.9 

73.6 

26.3 

26  3 

73.6 

26.3 

26,3 

'344 

66.7 

60,5 

6.2 

9.3 

34.5 

32.2 

48  3 

345 

77.6 

63.8 

13.8 

17.8 

63.8 

13.8 

17,8 

"347 

68.6 

56.6 

12.0 

17.5 

56.6 

12.0 

17.5 

348 

73.1 

64.4 

8.7 

11.9 

64.4 

8.7 

11.9 

349 

79.9 

68.2 

11.7 

14.6 

66.2 

13.7 

17.1 

351 

82.2 

69.9 

12.3 

15.0 

69.9 

12.3 

15.0 

352 

86.7 

69.0 

17.7 

20.4 

67.8 

18.9 

21,8 

356 

98.1 

88.2 

9.9 

10.1 

87.0 

11.1 

11,3 

"357 

95.8 

68.1 

27.7 

28.9 

68.1 

27.7 

28,9 

358 

102.6 

86.6 

16,0 

15.6 

86.6 

16.0 

15  6 

359 

70.8 

58  7 

12,1 

17.1 

58.7 

12.1 

17  1 

360 

84.9 

78.8 

6,1 

7.2 

75.7 

9.2 

10,8 

361 

68.6 

62.1 

6.5 

9.5 

60.4 

8.2 

12,0 

"364 

45.9 

43.4 

2.5 

5.4 

43.4 

2.5 

5.4 

365 

41.0 

40.9 

0.1 

0.2 

40.9 

0.1 

0.2 

366 

64.9 

61.7 

3.2 

4.9 

58.5 

6.4 

9.9 

367 

49.5 

41.4 

8.1 

16.4 

41.4 

8.1 

16.4 

"369 

104.9 

80.4 

24.5 

23.4 

80.4 

24.5 

23  4 

370 

65.4 

63.5 

1.9 

2.9 

63.5 

1.9 

2.9 

"372 

60.9 

50.7 

10,2 

16.7 

43.1 

17.8 

29.2 

376 

84.5 

59.1 

25.4 

30.1 

59.1 

25.4 

30.1 

377 

31.5 

31.0 

0.5 

1.6 

31.0 

0.5 

1.6 

378 

80.8 

61.7 

19.1 

23.6 

.54.7 

26.1 

32  3 

379 

93.5 

75.8 

17.7 

18  9 

71.8 

21.7 

23.2 

"381 

71.2 

52.7 

18.5 

26.0 

50.6 

20.6 

28.9 

382 

44.1 

38.0 

6.1 

13.8 

38.0 

6.1 

13,8 

386 

84.5 

66.8 

17.7 

20.9 

66,8 

17.7 

20.9 

"387 

55.0 

44.8 

10.2 

18.5 

44.1 

10.9 

19.8 

"  Dead. 


DISCUSSION    OF   RESULTS   AND    GENERAL   CONCLUSIONS. 


101 


Table  116. — Losses 

ill  body-weight  by  diabetics — Continued. 

(a)                     ('') 
Grimiest     i   Weight  at 

■   ui.       '     our  iirst 

T\  eight.       observation. 

Loss  in  weight  previous 
to  observation. 

(«) 

Maximum  loss  in  weight. 

Case  No. 

Minimum 

weight 
observed. 

1 

(c) 

id) 

(f) 

1 
(?)           1 

Amount 

Per  cent 

Amount 

Per  cent     i 

ia-b). 

(c-i-a). 

(a-e). 

(/-a).       i 

kilos. 

kilos. 

kilos. 

kilos. 

kilos. 

! 

390 

69.0 

65.4 

3.6 

5.2 

64.5 

4.5 

65        j 

391 

73.1 

80.7 

+  7.6 

+10.4 

80.7 

+  7.6 

+10.4 

392 

84.0 

78.6 

5.4 

6.4 

70.8 

13.2 

15  7 

394 

77.6 

63.6 

14.0 

18.0 

61.6 

16  0 

20,6        1 

'396 

93  5 

82.5 

11.0 

11.8 

82,5 

11  0 

11  8 

398 

79.0        !          82.8 

+  3.8 

+  4.8 

82.8 

+  3.8 

+  4,8 

399 

80  8                  64.3 

16.5 

20.4 

63.7 

17.1 

21  2 

'400 

59.0                 45.7 

13.3 

22.5 

40.9 

18.1 

30,7 

401 

45.9                 45.2 

0.7 

1.5 

45.2 

0  7 

1.5 

402 

61.8        1          55.6 

6.2 

10.0 

46.5 

15.3 

24  8 

403 

83.1        '          64.2 

18.9 

22.7 

64.2 

18.9 

22  7 

405 

49.5        '          47.6 

1.9 

3.8 

46.4 

3.1 

6.3 

408 

82.2        '          55.0 

27.2 

33.1 

55.0 

27.2 

33  1 

409 

78.6        '          77.6 

1.0 

1.3 

76.4 

2.2 

2  8 

411 

77.6                  78.5 

+  0.9 

+  1.2 

78.5 

+  0.9 

+  1.2 

413 

95.8                  68.6 

27.2 

28.4 

68.6 

27.2 

28.4 

'414 

53.4                 43.6 

9.8 

18.4 

43.6 

9.8 

18  4 

420 

69.9                  63.8 

6.1 

8.7 

63.8 

6,1 

8.7 

421 

94.9                  76.2 

18.7 

19.7 

76.2 

18.7 

19.7 

424 

79.9        1          63.8 

16.1 

20.2 

63.8 

16.1 

20.2 

428 

72.2        i          70.5 

1.7 

2.4 

70.5 

1.7 

2.4 

429 

98.1                  68.8 

29.3 

29.9 

68.8 

29.3 

29,9 

430 

72.2                 .54.7 

17.5 

24.2 

51,3 

20.9 

28  9 

431 

75  4                  69.5 

5.9 

7.8 

69.2 

6.2 

8  2 

432 

98.1        ;          80.4 

17.7 

18.0 

80.4 

17.7 

18  0 

'433 

65.4                  46.4 

19.0 

29.1 

41.4 

24.0 

36.7 

434 

20.2        '          18.7 

1.5 

7.4 

18.7 

1.5 

7.4 

435 

68  6        {          56  5 

12.1 

17.6 

56.5 

12.1 

17.6        1 

436 

67.7                  65.2 

2.5 

3.7 

63  0 

4  7 

6.9        .i 

'439 

58.6        i          45.6 

13  0 

22.2 

45.6 

13.0 

22.2        1 

'440 

73.1        :          57.2 

15.9 

21.8 

54.9 

18.2 

24.9        1 

442 

55.0        :          .58.4 

+  3.4 

+  6.2 

58  4 

+  3  4 

+  6.2 

443 

92.2                  78.4 

13.8 

15.0 

78.4 

13.8 

15.0 

444 

70.8        1          61.4 

9.4 

13.3 

61  4 

9.4 

13.3 

415 

92.2                 86.1 

6.1 

6.6 

86.1 

6,1 

6  6 

447 

69.9                  70.7 

+  08 

+  11 

70.7 

+  0,8 

+  1.1 

448 

68  6                 55.7 

12.9 

18.8 

55.7 

12  9 

18.8 

449 

68.6                 53.2 

15.4 

22.5 

49.8 

18.8 

27.4 

450 

85.4                  83.4 

2.0 

2.3 

79.7 

5.7 

6.7 

451 

76.3        '          44.1 

32.2 

42.2 

41.5 

34.8 

45  6 

452 

48.2                  40.4 

7.8 

16.2 

35  4 

12  8 

26.6 

453 

86.7        ;          61.8 

24  9 

28.7 

58.6 

28  1 

32.4 

454 

93.5        i          65.5 

28.0 

29.9 

61  6 

31.9 

34,1 

455 

99,0        i          96.8 

2.2 

2.2 

96  2 

2.8 

2,8 

'456 

77.6        1          65.4 

12.2 

15.7 

65.4 

12  2 

15.7 

457 

71.8        1          69.7 

2.1 

2.9 

61.9 

9  9 

13.8       ; 

459 

75.4        i          71.8 

3.6 

4.8 

71.8 

3.6 

4.8        ' 

462 

99.4        1        100.8 

+  1.4 

+  1.4 

96.5 

2.9 

2.9 

464 

84.5        '          61.9 

22.6 

26.7 

61.9 

22.6 

26.7 

466 

67.2        1          67.3 

+  0.1 

+  0.1 

67.3 

+  0.1 

+  0.1 

467 

73.1                  64.8 

8.3 

11.4 

64.0 

9  1 

12.4 

469 

66  3        1          53.7 

12.6 

19.0 

53.7 

12.6 

19.0 

472 

63.1                  54  1 

9.0 

14.3 

51.7 

11.4 

18.1 

'473 

77.6        j          58.5 

19.1 

24.6 

58,5 

19,1 

24.6           ; 

»Dead. 

which  is  due  almost  exclusively  to  a  loss  of  water  and  may  result  from  a  dietetic 
alteration  involving  the  withdrawal  of  carbohydrates  from  the  body  in  an 
effort  to  make  the  patient  sugar-free ;  second,  a  persistent  and  regular  loss  in 
body-weight  covering  a  period  of  several  months,  which  is  due  to  a  deficient 
energy  supply  caused  by  non-assimilation  and  an  insufficient  oxidation  of  food. 
The  case  is  furthermore  somewhat  complicated  by  the  fact  that  the  ingestion 
of  sodium  bicarbonate  may  actually  produce  a  gain  in  body-weight  which  is 
obviously  due  to  stored  water;  indeed,  we  have  still  another  complication  in  the 
fact  that  the  influence  of  the  retention  of  sodium  chloride  in  edema  may  become 
marked,  particularly  in  cases  of  diabetes,  with  defective  action  of  the  kidneys. 


102  METABOLISM   IN   SEVERE   DIABETES. 

It  is  safe  to  say,  therefore,  that  sudden  and  rapid  fluctuations  in  body-weight 
of  several  pounds  may  invariably  be  ascribed  to  changes  in  the  water-content 
of  the  body.  Persistent  and  regular  losses  in  body-weight  may  be  logically 
considered  as  conclusive  evidence  of  insufficient  available  calories  in  the  diet. 
This  insufficiency  may  be  due  to  a  non-assimilation  of  carbohydrates,  or  to  a 
defective  oxidation  of  fat  resulting  in  the  formation  of  /3-oxybutyric  and  allied 
acids.  In  any  event,  such  a  persistent  and  regular  loss  shows  that  the  patient 
is  not  getting  sufficient  food  for  daily  maintenance  and  drafts  are  being  made 
upon  body-material  to  supply  the  deficiency. 

Nitrogen  Excretion  of  Diabetics  without  Food. 

Inasmuch  as  certain  forms  of  artificially  induced  diabetes,  such,  for 
example,  as  pancreatic  diabetes  in  dogs,  are  accompanied  by  an  increase  in  the 
total  disintegration  of  nitrogenous  tissue,  it  is  of  interest  to  note  to  what  extent 
nitrogenous  material  is  broken  down  and  excreted  in  the  body  of  severe  dia- 
betics when  food  is  not  being  taken.  Accordingly,  during  the  period  of  every 
experiment  without  food,  the  urine  was  collected  usually  from  the  first  hour  of 
rising  in  the  morning  until  the  end  of  the  experimental  period  some  time  in  the 
middle  of  the  forenoon  or  later.  This  sample  of  urine,  which  thus  represented 
the  urine  excreted  during  the  experimental  period,  was  analyzed  both  for  nitro- 
gen and  for  sugar,  and  it  is  evident  that  the  total  excretion  of  nitrogen  here  may 
be  taken  as  a  measure  of  the  normal  excretion  of  nitrogen  of  the  individual 
when  not  actively  engaged  in  processes  of  digestion. 

The  determinations  of  the  nitrogen  on  the  basis  of  milligrams  per  hour  per 
kilogram  of  body-weight  are  given  for  all  the  later  experiments  in  table  117. 
The  average  value  is  8.4  mg.  per  kilogram  per  hour.  In  the  first  series  of 
experiments,  the  average  for  all  cases  was  9.4  mg.  per  hour.  The  average  for 
all  the  experiments  from  1908  to  1912  gave,  with  diabetics  both  light  and  severe, 
8.9  mg.  of  nitrogen  per  kilogram  of  body-weight  per  hour. 

In  the  earlier  publication  the  average  for  the  relatively  few  normal  sub- 
jects there  used  gave  6.85  mg.  of  nitrogen  per  hour,  and  it  was  explained  that 
the  difference  between  the  normal  value  and  that  found  with  diabetics  could 
not  by  any  means  explain  the  enormous  increase  in  metabolism  found  with 
these  subjects.  Since  this  time  a  large  number  of  other  individuals  have  been 
studied  and  the  results  obtained  with  14  of  these,  which  are  given  in  table  118, 
show  on  the  average  a  nitrogen  excretion  of  6.8  mg.  per  hour  per  kilogram  of 
body-weight,  a  value  identical  with  that  given  in  the  earlier  report. 

As  an  examination  of  the  various  charts  will  show,  the  diabetic  subjects 
were  not  given  excessively  rich  nitrogenous  diets,  nor,  indeed,  was  the  total 
nitrogen  in  the  urine  excessively  large  in  any  case.  In  conformity  with  the 
advice  of  Cantani,  Naunyn,  and  others,  we  have  purposely  kept  our  patients 
upon  a  low-protein  diet.  This  has  been  done  hoping  thereby  to  render  the 
task  more  simple  of  keeping  the  urine  free  from  sugar,  or  at  least  of  keeping  the 
sugar  at  a  low  level.  The  low  protein  was  prescribed  not  because  of  the  pre- 
formed sugar  in  the  protein  molecules,  but  because  of  the  tendency  for  sugar  to 


DISCUSSION    OF   RESULTS   AND   GENERAL   CONCLUSIONS. 


103 


T.AJBLE  117. 


-Nitrogen  excretion  of  diabetics  per  kilogram  of  body-weight  per  hour  in  periods 
without  food,  1910-1911. 


Date. 

Hours. 

Milli- 
grams. 

Date. 

Hours. 

Milli- 
grama. 

Case  H: 

Apr.  22,  1910 

6 

8.4 

Case  R: 

May  12,  1911 

3 

11.6 

Case  I- 

Feb.  23,  1911 4 

9.5 

CaseS: 

May    18,  1910 

2 

5.5 

Case  M: 

Aug.  17,  1910 

3 

6.4 

CaseT: 

Feb.   14,  1911 

4 

8.3 

Case  N: 

Dec.    1,1910 

4 
4 
4 
4 
4 
4 
4 

10.4 
8.7 
15.7 
13.7 
10.7 
13.2 
12.1 

Feb.  16,  1911 

1            9.5 

Average 

8.9 

Dec.    3,  1910 

Dec.    5,1910 

CaseU: 

May   26,  1910 

Dec.     7,  1910 

3 
4 
3 
3 

& 

5  6 
8.3 
9.8 
10.1 

K    7 

Dec.  10,  1910   

Mar.   31,  1911 

Dec.  12,  1910 

Apr.      2,  1911  

Dec.  14,  1910                  

June      2,1911 

Average 

June  2  3   1911 3 

12.1 

Case  0: 

Sept.  22,  1910     

3 
2 
5 

6.9 
9.5 
4.2 

Average 

Case  W: 

May   13,  1910 

7  9 

3            4.9 
3            3.5 

Sept.  23,  1910 

Sept.  24,  1910 '                 ... 

May   24,  1910 

Average 

Average 

6.9 

4.2 

Case  P: 

Sept.  25,  1911 

Sept.  29,  1911 

3 
3 
2 

2 

12.9 
9.2    1 
10.4    1 
in  ^ 

CaseX: 

Feb.  28,   1910  

5          10.8 

5  11  5 

6  7.0 

Mar.     1,  1910 

Oct.     9,  1911                .           .... 

Mar.   17,  1910 

Oct     10   19112 

Average  

Oct.    16,  1911 

3      j     16.4 

9.8 

Average 

.. 

11.9 

Total    average  of  experiments 

8.4 
9.4 
8.9 

Case  Q: 

Nov.  19,  1910 

4 
4 

8.7 
3.7 

Average  of  experiments  1908- 
1910 

Nov.  23,  1910 

Average  of  experiments  1998- 
1911 

Average 

6.2 

1  Nitrogen  excreted  between  2*'  IS""  and  1^  00"  a.m. 

2  Nitrogen  excreted  between  5'^  48""  and  1^  52™  a.m. 

'Nitrogen  excreted  between  10*^  30™  p.m.,  June  2,  and  6°  2.5™  a.m.,  June  3. 

Table  118. — Nitrogen  excretion  of  normal  subjects  per  kilogram  per  hour 
in  periods  without  food. 


Subject. 

Body- 
weight 
(without 
clothing) . 

No.  of    Average 
experi-     nitrogen 
ments.    excretion. 

Subject. 

Body- 
weight 
(without 
clothing). 

No.  of 
experi- 
ments. 

Average 
nitrogen 
excretion. 

F.G.B... 
J.  R    

kilos. 
82.5 
70.6 
66.3 
64.6 
63  4 
60.5 
60.4 

mg. 

1  6.7 

2  6.2 

H.L.H 

H.  F.T 

Dr.  S 

kilos. 
59.6 
58.6 
58.5 
58.1 
56.4 
64.5 
47.7 

3 
2 
5 
3 
1 
8 
3 

mg. 
7.9 
7.2 
5  6 
8.6 
4.9 
6.0 
6.2 

Dr   H 

2 
14 

1 
6 
6 

4.8 
5.7 
8  7 
7.5 
8.9 

J.  J.  C... 
D.  M 

D.J.M 

A.G.E 

V.  G 

F.  M.  M.. 
L.  E  E... 

T.  M.  C 

be  formed  from  the  amino-acid  radicles  in  the  protein.  It  was  also  felt  unwise 
to  increase  still  further  the  metabolism,  which  was  already  high  because  of  the 
disease  itself.  Finally,  from  a  prophylactic  point  of  view,  it  appeared  advisa- 
ble to  spare  the  overburdened  kidneys.  On  the  other  hand,  we  have  not 
attempted  to  prescribe  an  excessively  low-protein  intake,  because  in  an  earlier 
case  this  was  done  and  apparently  with  harm  to  the  patient.    It  would  be  most 


104  METABOLISM   IN   SEVERE   DIABETES. 

desirable  to  control  the  clinical  experience  of  Cantani,  Naunyn,  von  Noorden, 
and  others  by  experiments  upon  diabetics  with  a  low-protein  and  with  a  high- 
protein  intake,  and  this  we  hope  at  some  time  to  do. 

It  is  important  in  this  cormection  to  note  that  the  protein  metabolism  of 
these  diabetics  was  not  abnormally  great,  and  hence  we  have  not  here  to  deal 
with  anything  approximating  an  excessive  specific  dynamic  action  due  to  the 
disintegration  of  body  protein  as  a  result  of  the  disease. 

Gaseous  Metabolism. 
carbon  dioxide  excretion  in  diabetes. 

The  earliest  factor  in  the  gaseous  metaboUsm  of  diabetic  patients  to  be 
quantitatively  measured  was  the  carbon-dioxide  production,  and  this  was 
determined  by  the  Pettenkofer-Voit  chamber  with  great  accuracy.  The  same 
type  of  apparatus  was  used  even  as  late  as  1910  by  Dubois  and  Veeder  under 
the  direction  of  Brugsch.  As  was  pointed  out  in  our  earlier  report,  the  rela- 
tionship between  the  carbon-dioxide  excretion  and  the  heat  production  was 
so  accurately  established  by  our  experiments  with  the  calorimeters  that  the 
carbon-dioxide  measurement  acquired  thereby  a  new  significance. 

In  discussing  the  carbon-dioxide  production  of  diabetics  in  this  report,  it 
seems  desirable  to  present  again  the  observations  previously  reported,^  but  in 
this  instance  emphasizing  the  average  carbon-dioxide  production  not  of  all 
cases,  but  only  of  such  as  were  classified  as  severe.  These  data  are  given  in 
table  119,  in  which  the  carbon-dioxide  production  of  diabetics  in  experiments 
without  food  is  expressed  as  cubic  centimeters  per  kilogram  of  body-weight  per 
minute.  In  the  earlier  investigations,  the  chair  calorimeter,  the  bed  calorim- 
eter, and  the  respiration  apparatus  were  used  about  equally,  the  variations 
in  the  carbon-dioxide  production  as  measured  on  these  different  forms  of 
apparatus  being  shown  in  the  table.  As  was  previously  pointed  out,  the 
carbon-dioxide  production  as  determined  with  the  bed  calorimeter  and  the 
respiration  apparatus  was  essentially  the  same,  not  only  with  the  single  indi- 
viduals but  with  the  group  of  individuals.  On  the  other  hand,  with  the  chair 
calorimeter  there  was  a  considerable  increase  in  the  carbon-dioxide  production 
incidental  to  the  increase  in  muscular  tonus  because  the  subjects  were  sitting 
up  and  showed  greater  activity  in  general  when  inside  the  chair  calorimeter. 
The  values  for  the  moderately  severe  and  light  cases  of  diabetes,  although 
included  in  table  119,  do  not  need  special  discussion.  The  particularly  low 
value  found  for  Case  M  is  obviously  influenced  by  the  great  body-weight  of 
this  subject,  who  was  distinctly  fat.  On  the  average,  therefore,  with  severe 
diabetics,  the  carbon-dioxide  excretion  per  kilogram  of  body-weight  amounted 
to  3.53  c.c.  per  minute  of  carbon-dioxide  with  the  chair  calorimeter,  3.15  c.c. 
with  the  bed  calorimeter,  and  3.18  c.c.  with  the  respiration  apparatus.  The 
increase  of  approximately  10  per  cent  in  metabolism  noted  in  experiments  with 
the  chair  calorimeter  over  that  in  experiments  with  the  bed  calorimeter  and 

'Benedict  and  Joslin,  loc.  ciL,  p.  176. 


DISCUSSION    OF   RESULTS   AND    GENERAL   CONCLUSIONS. 


105 


the  respiration  apparatus  is  fully  in  conformity  with  the  increased  metabolism 
noted  with  normal  individuals  when  changing  from  a  lying  to  a  sitting  position.^ 
In  the  later  investigation  the  subdivision  of  experiments  is  almost  exclu- 
sively between  the  bed  calorimeter  and  the  respiration  apparatus,  there  being 
but  one  set  of  experiments  made  with  the  chair  calorimeter.  The  results  for 
all  the  cases  are  given  in  table  120.  Special  attention  is  dra\Mi  to  the  average 
carbon-dioxide  excretion  of  the  severe  cases.  Unlike  the  results  given  in  the 
earlier  report,  the  experiments  with  the  bed  calorimeter  apparently  show  a  con- 
siderably higher  average  value  than  does  the  respiration  apparatus,  i.  e.,  3.64 
c.c.  against  3.24  c.c.  A  close  inspection  of  the  figures  shows,  however,  that  the 
value  for  the  bed  calorimeter  is  distinctly  affected  by  the  abnormally  high 
values  of  Cases  I  and  N.     It  is  also  due  to  the  fact  that  in  practically  no  case 

Table  119. — Carbon  dioxide  eliminated  per  kilogram  of  body-weight  per  minute  by  diabetics  in 
experiments  without  food,  1908-1910. 


Subject. 

Chair  calorimeter.                   Bed  calorimeter. 

Respiration  apparatus. 

Carbon  dioxide 
eliminated. 

Aver- 
age. 

Carbon  dioxide 
eliminated. 

Aver- 
age. 

Carbon  dioxide 
ehminated. 

Aver- 
age. 

Severe  diabetes. 
Case  A 

3.38    3.05    3.25 
3.37    3.52    3.20 

3.43  3.03    3.29 

3!i5    3!22    3^14 
3.22    3  15    3.03 
3.14    3.24 

3AQ    z.ik    '.'.'.'. 

3.44    

4.32    4.31     .... 
3.72    

c.c. 
3.28 

3!i6 

3^29 
3.44 

4.32 
3.72 

3.22    

3.23    

2.95    

c.c. 
3.22 

3.23 
2.95 

3!22 
3.12 

3.04    2.99    2.99    3.17 

2.79    2.78    2.89    2.60 

2.82    2.78    3.33    3.04 

3.21    2.92    2.83    2.85 

2.87 

3.25    3.08    3.00    .... 

3!64    '.'.'.'.     '.'.'.'.     '.'.'.'. 

4!62  3;%  3:48  ;;;; 

2.84    

c.c. 

3.05 
2.90 

3.11 

3!64 
3!82 

B 

G 

D 

E 

3!22    '. 
3.24    3 
3.14    3 

08    2!94 
19 

F 

G 

H 

I 

J 

3!44    '.'.'.'.     '.'.'.'. 
2.57    

Av.  severe  cases     

3.53 

3  15 

3.18 

Light  diabetes. 
CaseK 

3.10    

3.10 
3.46 

2.37 

3!44 
2.57 

2.84 

L 

3.53    3.42    3.46 

3.42 

2.41    2.32    .... 

M 

Av.  light  cases. . 

2.98 

3.00 

2.84 

were  experiments  made  simultaneously  with  the  bed  calorimeter  and  the  respi- 
ration apparatus.  The  only  exception  to  this  is  Case  U,  where  the  value  of  3.88 
c.c.  with  the  bed  calorimeter  does  not  differ  widely  from  that  found  with  the 
respiration  apparatus,  namely,  3.79  c.c.  It  should  be  noted  that  these  averages 
neither  represent  an  equal  number  of  experiments  nor  comparison  experiments 
with  the  same  subject  in  the  two  different  forms  of  apparatus,  and  consequently 
do  not  in  any  way  vitiate  the  conclusion  dra\\Ti  from  the  earlier  experiments 
that  the  carbon-dioxide  production  with  the  same  individual  is  essentially  the 
same  whether  he  is  in  the  bed  calorimeter  or  lying  on  the  respiration  apparatus. 
Of  the  moderately  severe  and  light  cases,  Case  M  was  studied  both  with  the  bed 
calorimeter  and  the  respiration  apparatus,  giving  essentially  the  same  results. 


'Emmes  and  Riche,  Am.  Journ.  Physiol.,  1911,  27,  p.  406. 


106 


METABOLISM   IN    SEVERE   DIABETES. 


The  somewhat  higher  value  found  with  the  chair  calorimeter  for  Case  X  over 
that  found  with  the  respiration  apparatus  is  again  accounted  for  by  the  natural 
influence  of  change  in  position  and  muscular  tonus  incidental  to  sitting  up. 
For  the  purpose  of  securing  average  figures,  the  carbon-dioxide  produc- 
tion of  all  diabetic  subjects  thus  far  studied  by  us  with  the  chair  calorimeter, 
bed  calorimeter,  and  respiration  apparatus  has  been  collected,  averaged,  and 
presented  in  table  121.  On  inspecting  the  average  values  for  the  severe  cases 
it  is  again  seen  that  the  results  are  somewhat  complicated  by  the  fact  that  in 
the  first  place  the  same  number  of  individuals  were  not  studied  with  all  three 
different  forms  of  apparatus.  Secondly,  the  values  found  with  Case  I  in  the 
chair  calorimeter  were  obtained  nearly  a  year  prior  to  those  found  with  the 
same  case  in  the  bed  calorimeter,  during  which  time  the  disease  had  pro- 
gressed and  the  subject  was  in  a  much  more  critical  state  and  with  an  essen- 

Table  120. — Carbon  dioxide  eliminated  per  kilogram  of  body-weight  per  minute  by  diabetics  in 
experiments  without  food,  1910-1911. 


Subject. 

Chair  calorimeter. 

Bed  calorimeter. 

Respiration  apparatus. 

Carbon  dioxide 
eliminated. 

Aver- 
age. 

Carbon  dioxide 
eliminated. 

Aver- 
age. 

Carbon  dioxide 
eliminated. 

Aver- 
age. 

Severe  diabetes. 
Case  A 

C.C. 

3!6i  '.'.'.'.  '.'.'.'.  '.'.'.'. 

4.33 

4^26  S^Q?  3!97  4!66 
4.47  4.10  3.92 

3.42  3.29  

3.51 

3^32  3!26  '.'.'.'.   '.'.'.'. 
3.88 

2.29 



c.c. 

s.bi 

4.33 

4.ii 

3.36 
3.51 

3;29 
3.88 

2.89 

3^27  3^29  3!36  '.'.'.'. 
3.08 

3.14  3.15  2.89  .... 
3.69  3.68  3.67  3.96 
3.73 

2;64  '.'.'.'.   '.'.'.'.   '.'.'.'. 

Z.76  3.n  3'79  3^88 
3.42' 

2.41 

2.78  2.72  

2.82 

c.c. 
2.89 

3.08 

3.06 
3.75 

2:64 

379 
3.42 

H 

.... 

.... 
i     •••■ 

I 

K 

L 

N 

o 

P 

Q 

R 

s 

T 

U 

v.... 

Av.  severe  cases . 

Moderately  severe  and 
light  diabetes. 

CaseM 

1     .... 

3  64 

3.24 

! 

3^24 

2.29 

2.41 

2.75 

2  82 

W 

X 

3.53  3.25  2.93  .... 

Av.  moderately 
severe    and 

3.24 

2.29 

2.66 

>At  e*"  45™  a.m.  the  subject  ate  a  lis;ht  breakfast  consisting  of  a  2-egg  omelet  and  a  cup  of  coffee.    The  experiment 
began  at  9'>  22"  a.m.,  the  last  period  ending  at  ll*"  10™  a.m. 

tially  higher  metabolism,  although  with  considerably  less  extraneous  muscular 
activity.  Probably  an  average  of  the  results  obtained  with  the  bed  calo- 
rimeter and  the  respiration  apparatus  will  represent  more  nearly  the  grand  aver- 
age of  the  carbon-dioxide  production  of  subjects  with  severe  diabetes  lying 
quietly  at  rest.  This  average  value,  3.33  c.c.  per  kilogram  of  body-weight, 
may  be  taken  therefore  as  the  average  carbon-dioxide  production  of  subjects 
with  severe  diabetes.  The  number  of  cases  of  moderately  severe  and  light 
diabetes  are  too  few  from  which  to  draw  any  general  deductions,  although  a 
distinct  tendency  is  shown  for  the  carbon  dioxide  to  be  somewhat  lower  in 
these  cases. 


DISCUSSION    OF   RESULTS   AND    GENERAL   CONCLUSIONS. 


107 


Table  121. — Average  carbon  dioxide  eliminated  per  kilogram  of  body-weight  -per  minute  by 
diabetics  in  experiments  without  food,  1908-1911. 


Subject. 

Chair 
calorim- 
eter. 

Bed  calo- 
rimeter. 

Respiration 
apparatus. 

Subject. 

Chair 
calorim- 
eter. 

Bed  calo- 
rimeter. 

Respiration 
apparatus. 

Severe  diabetes. 

c 
3 

3 

3 
3 

4 
3 

c. 
28 

ie 

29 
44 

32 

72 

c.c. 
3.22 
3.23 
2.95 

322 
3.10 
4.33 

4;ii 

3.36 
3.51 

3^29 

c.c. 

2.89        1 
3.05 
2.90 
3.11 

3!64 

3!48 
3  31 
3.08 

3M 
3.75 

2^64 

Severe  diabetes — Con. 
Case  U . . .    . 

C.C. 

c.c. 
3.88 

c.c. 
3.79 

B 

V 

c 

Av.  severe  cases. . 

Av.  all  expt3.with 
bed  calorimeter 
and  respiration 
apparatus  

Moderately  severe 
diabetes. 

CaseK  (1909) 

L  (1909) 

W 

i       "•  *- 

D 

3  54            .1  d7      1        ^  19 

v 

. 

F 

3.33 

G 

H 

I 

J 

3.10 
3.46 

3!24 

K  (1910) 

L  (1910) 

N 

i'.ii 

2.84 

2;75 
2.82 

0 

P 

X 

Q 

Av.     moderately 
severe  cases. . . 

Light  diabetes. 

Case  M 

R 

3.27 

■    -i               1 

S 

2.44 

2.80 

T 

2.37 

2.43 

2  41 

OXYGEN  CONSUMPTION  IN  DIABETES. 

The  quantitative  measurement  of  the  oxygen  consumption  of  diabetics  has 
been  attempted  only  by  means  of  the  Zuntz-Geppert  apparatus/  by  Weintraud 
and  Laves  with  the  Hoppe-Seyler  apparatus,^  and  by  us^  in  our  earlier  investi- 
gations.'* The  difficulties  incidental  to  the  accurate  determinations  of  the  oxy- 
gen consumption  have  precluded  a  more  general  measurement.  On  the  other 
hand,  exact  determinations  of  the  oxygen  used  by  the  subject  have  greater 
significance  as  an  index  of  the  calorific  output  of  the  body  than  have  the  deter- 
minations of  the  carbon-dioxide  excretion,  especially  with  normal  individuals. 
With  diabetics,  as  we  have  shown  earlier,  particularly  with  severe  cases,  the 
carbon-dioxide  determinations,  if  accurately  made,  may  be  considered  equally 
as  good  an  index  of  the  heat  production  as  is  the  oxygen.  Nevertheless  it 
remains  a  fact  that  quantitative  determinations  of  oxygen  have  a  special  sig- 
nificance and  are  of  unusual  importance  and  interest.  Since  especial  emphasis 
is  laid  in  this  report  upon  the  severity  of  diabetes,  in  connection  with  the  dis- 
cussion of  the  metabolism  during  diabetes  mellitus  we  have  deemed  it  advis- 
able in  table  122  to  present  again  the  oxygen  determinations  obtained  in  our 
earlier  investigations,  accentuating  here  the  oxygen  determinations  found  -Rath 
the  severe  cases  rather  than  the  total  average. 

»Leo  (1891),  Stuve  (1894),  Nehring  and  SchmoU  (1897),  Magnus  Levy  (1905),  Mohr 
(1907). 

'Weintraud  and  Laves,  Zeitsclir.  f.  physiol.  Chem.,  1894,  19,  p.  603. 

•  Benedict  and  Joslin,  Publication  No.  136,  Carnegie  Institution  of  Washington,  1910. 

■•Two  articles  have  recently  appeared  giving  reports  of  studies  made  by  Roily  and  by 
Leimdorfer  of  the  oxygen  consumption  of  diabetics.  Unfortunately  these  did  not  come  to 
our  attention  until  after  this  report  had  been  sent  to  the  printer,  and  therefore  scant  com- 
ment only  is  possible  in  the  proof.  Roily  in  Leipsic  used  a  modified  Benedict  respiration 
apparatus.  See  Roily,  Deutsch.  Archiv  f.  klin  Med.,  1912,  105,  p.  494.  Leimdorfer  in  von 
Noorden's  laboratory  used  the  Zuntz-Geppert  method.  See  Leimdorfer,  Biochem.  Ztschr., 
1912,  40,  p.  326. 


108 


METABOLISM   IN   SEVERE   DIABETES. 


The  agreement  between  the  results  found  with  the  bed  calorimeter  and 
those  with  the  respiration  apparatus  is  obvious,  the  greater  increase  noted  with 
the  chair  calorimeter  being  explained  in  part  by  the  fact  that  there  is  an  actual 
increase  in  the  metabolism  due  to  the  sitting  up  in  the  chair,  and  in  part  to  the 
fact  that  the  abnormally  high  values  found  with  Cases  I  and  J  were  not  accom- 
panied by  similar  experiments  with  either  the  bed  calorimeter  or  the  respiration 
apparatus.  From  this  earlier  work,  therefore,  one  can  conclude  that  for  sub- 
jects with  severe  diabetes,  lying  quietl}',  without  food,  there  is  approximately  a 
consumption  of  4.22  c.c.  of  oxygen  per  minute  per  kilogram  of  body-weight. 

Table  122. — Oxygen  absorbed  per  kilogram  of  body-weight  per  minute  in  experiments  with 
diabetics  u-ithout  food,  1908-1910. 


Chair  calorimeter. 

Bed  calorimeter. 

Respiration  apparatus. 

Subject. 

Oxygen  absorbed. 

Aver- 
age. 

Oxygen  absorbed. 

Aver- 
age. 

Oxygen  absorbed. 

Aver- 
age. 

Severe  diabetes.     \ 
Case  A i    4.86    4.34    4.38 

c.e. 
4.62 

4!45 

4!53 
4.66 

5.82 
5.01 

4.22    

4.42     

4.15    

4!38    '.'.'.'. 

4.34    3.88    3.63 

4.32    4.17 

c.c. 
4.22 

4.42 
4.15 

4.38 
4.07 

4.27    4.04    4.31    4.47 

4.01     4.44    4.08    3.82 

4.23    3.93    4.85    4.28 

4.52    4.44    4.19    4.06 

4.14 

4.44    4.14    4.00    .... 

i'.bi    '.'.'.'.     '.'.'.'.     '.'.'.'. 
4.04     

c.c. 

4.27 
4.23 

4.19 

i'.oi 

4.92    4.86    4.50 
5.17    4.13    4.44 

B 

C '    4.20    4.31    4  72 

i    4.80    4.55    4.08 
4.40    4.54 

D 

E 1    4.73    4.32     .... 

F 1    4.66    

G !    

H i    

1 5.65    5.98    .... 

J 5.01     

Av.  severe  cases     

Light  diabetes. 
Ca.se  K '    4.06    

4.85 

i.ii    '.'.'.'.     '.'.'.'. 
3.28    

4.25 

4.18 

4.06 

4!4i 
3.28 

4.04 

L f    4.55    4.58    4.64 

1    4.35 
M j    3.09    3.20    .... 

4.53 
3.15 

A  V.  light  cases..!    

3.91 

3.85 

4.04 

The  later  experiments  were  almost  exclusively  made  with  either  the  bed 
calorimeter  or  the  respiration  apparatus.  The  results  obtained  in  these  experi- 
ments are  given  in  table  123  herewith.  As  was  pointed  out  in  our  discussion 
of  the  carbon-dioxide  consumption,  the  agreement  between  the  average  results 
found  with  the  bed  calorimeter  and  the  respiration  apparatus  is  not  what 
would  be  expected,  because  the  abnormally  high  values  of  subjects  I  and  N 
as  determined  in  the  bed  calorimeter  are  not  accompanied  by  similar  obser- 
vations on  the  same  subject  with  the  respiration  apparatus.  Likewise,  the 
recent  experiments  differ  from  the  earlier  investigations  chiefly  in  the  fact  that 
with  practically  no  subject  were  experiments  made  with  both  the  bed  calo- 
rimeter and  the  respiration  apparatus;  therefore  the  comparison  is  obviously 
not  as  simple  as  it  was  in  the  earlier  report.  If  we  consider  the  average  of  the 
results  found  with  the  cases  of  severe  diabetes  in  the  bed  calorimeter  and  on  the 
respiration  apparatus  as  representing  the  truest  average,  we  may  state  that 
with  these  subjects  lying  quietly  at  rest  without  food,  4.73  c.c.  of  oxygen  are 


DISCUSSION    OF   RESULTS   AND    GENERAL    CONCLUSIONS. 


109 


absorbed  per  kilogram  of  body-weight  per  minute.  The  paucity  of  experi- 
mental data  with  regard  to  light  cases  prevents  any  general  deduction,  although 
it  is  again  obvious  that  there  is  on  the  average  a  much  smaller  oxygen  con- 
sumption per  kilogram  of  body-weight  than  with  the  severe  cases.  Finally,  it 
should  be  noted  that  in  the  experiment  with  Case  X,  the  value  found  with  the 
chair  calorimeter  (4.17  c.c.)  is  higher  than  that  found  with  the  respiration 
apparatus  (3.79  c.c.)  and  can  be  wholly  explained  by  the  difference  in  the  mus- 
cular activity  incidental  to  experiments  in  the  chair  calorimeter. 

Table  123.— Oxygen  absorbed  per  kilogram  of  body-weight  per  minute  by  diabetics  in  experi- 
ments without  food,  1910-1911. 


Subject. 

Chair  calorimeter. 

Bed  calorimeter. 

Respiration  apparatus. 

Oxygen  absorbed. 

Aver- 
age. 

Oxygen  absorbed. 

Aver- 
age. 

Oxygen  absorbed. 

Aver- 
age. 

Severe  diabetes. 
Case  A 

c.c. 

3;97 ;;;; .'.'.'. .'..'. 

6.03 

5;74  i.25  h'.Z9  5!56 
5.88  5.71  5.54 

4.51  4.23  

4.90 

4!66  4.35  '.'.'.'.   '.'.'.'. 
2.93 

c  c. 
6.03 

5:57 

4.37 
4.90 

4.08 

4;62  4^57  i;??  '.'.'.'. 
4.23 

4.28  4.44  4.01   .... 
5.26  5.24  5.40  5.60 
5.22 

3!67  '.'.'.'.   '.'.'.'.   '.'.'.'. 

4  9o  b.2i  5.15  hAl 
4.721 

3.21 

3.91  3.62  

3.79 

c.c. 
4.08 

4165 
4.23 

4.24 
5.34 

3;67 

5126 
4.72 

H 

I 

K 

L 

N 

O 

P 

Q 

R :.:. 

S 

T 

U 

V 

Av.  severe  cases. 

Moderately  severe  and 
light  diabetes. 

CaseM 

4.89 

4  57 

4;i7 

2.93 

3.21 
3.77 
3.79 

W 

X 

4.80  4.08  3.62  .... 

Av.  moderatelj' 
severe        and 

4.17 

2.93 

3.59 

'At  6''  45""  a.m.  the  subject  ate  a  light  breakfast  consisting  of  a  2-egg  omelet  and  a  cup  of  coffee.    The  experiment 
began  at  9''  22™  a.m.,  the  last  period  ending  at  ll''  10™  a.m. 

In  table  124  are  given  the  averages  of  the  values  found  in  both  series  of 
experiments  with  the  different  subjects  and  with  the  different  forms  of  experi- 
mental apparatus,  i.  e.,  the  bed  calorimeter,  chair  calorimeter,  and  respiration 
apparatus,  these  showing  that  4.85  c.c.  of  oxygen  were  absorbed  and  measured 
in  the  chair  calorimeter,  4.66  c.c.  with  the  bed  calorimeter,  and  4.41  c.c.  with 
the  respiration  apparatus.  Admitting  that  the  chair-calorimeter  results  are 
affected  somewhat  bj-  increased  muscular  activity  incidental  to  experiments  in 
this  apparatus,  we  may  average  the  results  found  in  the  Ijcd  calorimeter  and  the 
respiration  apparatus  and  consider  the  average  value  of  4.54  c.c.  per  minute  as 
the  best  average  value  for  severe  diabetics  lying  quietly  at  rest  without  food. 
The  subjects  with  moderately  severe  and  light  diabetes  have  relatively  less 
oxygen  consumption  under  the  same  conditions,  although  in  this  discussion 
attention  is  particularly'  directed  to  the  values  found  with  the  severe  cases. 


110 


METABOLISM   IN   SEVERE   DIABETES. 


Table  124. 


-Average  oxygen  absorbed  per  kilogram  of  body-weight  per  minute  in  experiments 
with  diabetics  without  food,  1908-1911. 


Subject. 

Chair 
calori- 
meter. 

Bed 
calori- 
meter. 

Respiration 
apparatus. 

Subject. 

Chair 
calori- 
meter. 

Bed 
calori- 
meter. 

Respiration 
apparatus. 

Severe  diabetes. 
Case  A     

c.c. 
4.62 

4!45 

4!53 
4.66 

5^82 
5.01 

c.c. 
4.22 
4.42 
4.15 

4;38 
4.05 
6.03 

5!57 
4!37 

c.c. 
4.08 
4.27 
4.23 
4.19 

4!63 

4;54 
4.65 
4.23 

5.34 

Severe  diabetes — Con. 
Case  U 

c.c. 

c.c. 

c.c. 
5.20 
4.72 

B 

V 

r« 

Av.  severe  cases. . 

Av.  all  expts.with 
bed  calorimeter 
and  re.spiration 
apparatus 

Moderately  severe 
diabetes. 

CaseK  (1909) 

L  (1909) 

W 

D 

4.85 

4.66      1       4.41 

E 

4.54 

F 

G 

H 

I 

J 

4.06 
4.53 

4;i7 

4!4i 

4.04 
3.79 

K  (1910) 

L  fl910) 

N 

0 

P 

X 

Q 

Av.  moderately- 
severe  cases . . . 

Light  diabetes. 

CaseM 

R 

4.90      1 

3.67 
4.51 

1 

3.87 

s 

4.25 

4.41 

T 

.... 

3.15 

3.11 

3  21 

RESPIRATORY  QUOTIENT. 

The  relationship  between  the  volume  of  carbon  dioxide  produced  and 

oxygen  consumed  (  -— ^  ) ,  the  so-called  respiratory  quotient,  has  peculiar  sig- 

niJBcance  in  interpreting  the  degree  of  severity  in  cases  of  diabetes.  The  accu- 
racy of  this  value  depends  upon  the  accuracy  of  both  the  determination  of 
carbon  dioxide  and  the  determination  of  oxygen,  and  it  can  thus  be  seen  that 
the  respiratory  quotient  as  such  is  a  difficult  matter  to  determine  with  great 
exactness.  In  the  earlier  report  the  respiratory  quotient  for  all  the  cases  of 
diabetes  was  considered  in  detail  and  in  table  125  we  have  presented  anew  the 
earlier  work,  carefully  distinguishing  between  the  severe  cases  and  the  lighter 
cases. 

In  recording  the  results  for  the  respiratory  quotient,  it  is  unnecessary  to 
consider  separately  those  obtained  with  the  three  forms  of  apparatus,  for  there 
is  no  physical  difference  in  the  respiration  in  either  the  chair  or  the  bed  calori- 
meter, and  obviously  the  character  of  the  combustion  and  the  material  burned 
or  metabolized  will  not  be  appreciably  altered  by  different  body  positions.  On 
the  other  hand,  it  is  reasonable  to  suppose  that  the  carbon-dioxide  production 
and  oxygen  consumption  might  indicate  a  difference  in  the  character  of  the 
combustion,  according  to  whether  the  subject  breathed  freely  in  the  calori- 
meter, or  whether  he  breathed  into  the  nosepieces  or  mouthpiece  of  the  respi- 
ration apparatus.  Accordingly,  in  giving  the  results  of  the  earlier  experiments, 
the  values  obtained  with  the  calorimeter  are  compared  with  those  obtained 
with  the  respiration  apparatus.  It  can  be  seen  that  the  respiratory  quotient 
in  the  severe  cases  of  diabetes  averages  0.74  with  the  calorimeter  and  0.73  with 
the  respiration  apparatus.  The  fact  that  there  are  not  an  equal  number  of 
experiments  made  with  the  same  subject  on  both  apparatus  complicates  some- 


DISCUSSION    OF   RESULTS   AND   GENERAL   CONCLUSIONS. 


Ill 


what  the  comparison.  Particularly  is  this  true  with  subjects  having  light 
diabetes  with  whom  an  average  quotient  of  0.76  was  obtained  in  the  chair  cal- 
orimeter, while  apparently  a  quotient  of  0.70  was  found  with  the  respiration 
apparatus.  An  examination  of  the  figures  shows,  however,  that  the  second 
value  depends  wholly  upon  a  single  experiment  wdth  Case  K,  and  hence  as  an 
average  value  is  very  much  to  be  questioned.  The  important  thing  to  be 
emphasized  here  is  the  fact  that  there  were  no  abnormal  quotients  found, 
although  a  single  value  of  0.64  was  found  with  Case  C  and  one  of  0.66  with 
Case  A.  In  general,  however,  none  of  the  abnormally  low  quotients  which 
have  frequently  been  cited  by  earlier  writers  were  found;  at  least  there  was  no 
persistent  evidence  of  an  abnormal  katabolism  which  such  low  quotients 
would  indicate. 

Table  125. — Average  respiratory  quotients  in  experiments  with  diabetics  without  food 

1908-1910. 


Subject. 

Calorimeter. 

Respiration  apparatus. 

Respiratory  quotient. 

Average. 

Respiratory  quotient. 

Average. 

Severe  diabetes. 

0.75    0.75    0.74    0.76 
0.68    0.72    0.71    0.66 
0.73    0.74 

0.74     

0.75    0.75    0.67    0.69 
0.69    0.74    0.71    0.71 
0.72 

6!72    6!74    .'.'."     '.'.'.'. 

0.74    

0.73    

0.75    0.79    0.81    0.72 
0.76 

0,76    0.72    

0.75    

0.76     

0.78    0.75    0.75    0.78 

0.79 

0.78    0.78    0.72    .... 

0.71 

0.74 
0.71 

6!73 
0.74 
0.73 
0.77 

0.74 
0.75 

0.71    0.75    0.70    

0.70    0.64    0.71    0.68    0.67 
0.71    0.69    0.71    0.71    0.66 
0.68    0.70    0.69 
0.73    0.74    0.75     

6^76  '.'.'.'.  '.'.'.'.  '...'.  ;;;; 

0.70    

0.72 
0.69 

0.74 
6!76 

B 

C 

D 

E 

F 

G 

H 

I 

J 

Av.  severe  cases 

Light  diabetes. 
Case  K 

0.74 

0.73 

0.76 
0.77 

0.76 

0.70 

L 

M 

Av.  light  cases 

0.76 

0.70 

It  should  be  pointed  out  again  that  the  respiratory  quotient  is  entirely 
independent  of  the  total  metabolism,  and  indicates  only  the  character  of  the 
metabolism  and  not  the  total  amount.  When  the  body  is  subsisting  chiefly 
upon  carbohydrates,  the  respiratory  quotient  approximates  1.  When  it  is 
subsisting  chiefly  upon  fat,  the  respiratory  quotient  approximates  0.71.  The 
quotients,  therefore,  here  observed  with  severe  diabetes  indicate  a  combustion 
which  is  chiefly  that  of  fat.  Inasmuch  as  the  relatively  small  amounts  of 
protein  burned  tend  to  raise  the  quotient,  we  find  the  average  values  slightly 
above  0.71  rather  than  slightly  below. 

The  respiratory  quotients  for  the  new  series  of  experiments  are  given  in 
table  126.  These  quotients,  which  are  classified  as  severe  cases  and  moder- 
ately severe  and  light  cases,  indicate  again  a  low  respiratory  quotient  as  the 
characteristic  of  severe  diabetes,  the  average  quotient  found  with  the  calori- 


112 


METABOLISM   IN    SEVERE   DIABETES. 


meter  being  0.73  and  with  the  respiration  apparatus  0.72,  values  not  appre- 
ciably different  from  those  obtained  in  the  earlier  series.  As  a  matter  of  fact, 
the  lowest  individual  respiratory  quotient  found  in  the  new  series  of  experi- 
ments was  the  value  0.68  obtained  with  Case  P  in  one  experiment. 

The  moderately  severe  and  light  cases  are  too  few  in  number  for  us  to 
draw  any  deductions,  but  there  is  a  tendency  for  the  respiratory  quotient  to 
be  somewhat  higher  with  the  light  cases  than  with  the  severe,  thus  indicating  a 
slightly  higher  combustion  of  carbohydrate.  The  low  averages  found  with  the 
severe  cases  indicate  a  combustion  almost  exclusively  of  fat,  with  a  relatively 
small  amount  of  protein  and  almost  no  carbohydrate  combustion.     This  is 


Table  126.- 


-Average  respiratory  quotients  in  experiments  with  diabetics  without  food, 
1910-1911. 


Subjent. 

Calorimeter. 

Respiration  apparatus. 

Respiratory  quotient. 

Average. 

Respiratory  quotient. 

Average. 

Severe  diabetes. 

0.76 
0.72 

6^74 

0.69 
0.77 
0.72 

6;73 
■0.73 

0.71 

6'7i  o.ii  6!7i  '.'.'.'.  '.'.'.'.  '.'.'.'. 

0.73 



0.74  0.71  0.72  

0.70  0.70  0.68  0.71  0.71  .... 

6!73  '.'.'.'.   '.'.'.'.   '.'.'.'.   '.'.'.'.   '.'.'.'. 

6;76  6;7i  6.74  6^71  .'.'.'.'  '.'.'.'. 
0.732 

0.75 

0.72  0.75  

0.74 

0.71 

6^72 
0.73 

0.72 
0.70 

6!  73 

6.73 
0.73" 

H 

0.76 

0.72 

I 

K 

L 

N 

0.74  0.76  0.73  0.74  0.76  0.72 
0.71 

O 

P 

0.69 

0  76  0.78  

0.72 

6!7i  6!75  '.'.'.'.   '.'.'.'.   '.'.'.'.   '.'.'.'. 
0.73' 

Q 

R 

R 

T 

U 

V 

Av.  severe  cases 



0.73 

0.72 

Moderately  severe  and  light 
diabetes. 

0.78 

0.78 
6!78 

0.75 
0.74 
0.74 

W 

X 

6.73  6.80  6. si  

Av.  moderately  severe 

0.78 

0.74 

■The  respiratory  quotient  for  this  experiment  was  for  the  periods  ll''  55™  p.m.  to  l**  27™  a.m.  and  5**  05™  to 

6^  0.5™  a.m.,  June  2-3,  1911. 
2  At  6"  4.5™  a.m.  the  subject  ate  a  Ught  breakfast  consisting  of  a  2-egg  omelet  and  a  cup  of  coffee.    The  experiment 

began  at  9^  22™  a.m.,  the  last  period  ending  at  U**  10™  a.m. 

fully  in  conformity  with  the  verj^  low  carbohydrate  supply  in  the  bodies  of  dia- 
betics, and  it  is  fully  in  accord  with  what  theoretically  would  be  predicted. 
Here  again  we  find  a  complete  absence  of  the  abnormally  low  quotients  fre- 
quently reported  by  earlier  writers. 

In  order  to  sum  up  the  results  of  all  the  experiments  thus  far  made,  we 
have  computed  the  respiratory  quotients  for  each  individual  case  both  in  the 
calorimeter  and  with  the  respiration  apparatus  when  experiments  with  both 
apparatus  had  been  made,  and  they  are  combined  in  table  127.  It  is  seen  that 
the  average  value  with  severe  diabetes  in  both  the  calorimeter  experiments 
and  the  respiration  experiments  was  0.73,  although  here  again  it  should  be 
pointed  out  that  experiments  on  each  individual  were  rarely  performed  with 
both  apparatus. 


DISCUSSION    OF   RESULTS   AND   GENERAL   CONCLUSIONS. 


113 


It  may  be  concluded,  therefore,  that  with  the  subject  lying  quietly  without 
food  the  respiratory  quotient  in  cases  of  severe  diabetes  is  0.73;  as  pointed  out 
in  the  earlier  report,  respiratory  quotients  carefully  determined  that  indicate 
values  higher  than  this  are  to  be  considered  a  favorable  prognostic  indication, 
and  show  a  rather  more  liberal  supply  of  carbohydrate  material  in  the  body 
than  is  usual  in  severe  diabetes. 

The  difficulties  incidental  to  determining  accurately  the  respiratory  quo- 
tients are  only  too  well  known  to  experimenters,  and  hence  it  would  be  entirely 
incorrect  to  lay  great  stress  upon  individual  figures  in  this  series.  The  general 
tendency  of  all  the  quotients  to  approximate  the  value  0.73  is  significant,  as  is 
likewise  the  absence  of  abnormally  low  quotients. 

Table  127. — Average  res-piratory  quotients  in  experiments  with  diabetics  ivithout  food, 

1908-1911. 


Subject. 

Calori- 
meter. 

Respiration 
apparatus. 

Subject. 

Calori- 
meter. 

Respiration 
apparatus. 

Severe  diabetes. 

0.71 
0.74 
0.71 

6!73 
0.74 
0.73 
0.77 
0.73 
0  75 

0.71 
0.72 
0.69 
0.74 

6!  76 
6'77 

Severe  diabetes — Con. 
CaseT 

0.73 
0.73 

6!  7.3 
0.73 

B 

U 

c 

V 

Av.  severe  cases . . . 

Moderately  severe 
diabetes. 

Case  K  (1909) 

E 

0  73 

0  73 

F 

0.76 
0.77 

6!  78 

0.70 

o.ii 

0.74 

G 

H 

I 

J 

1            L  (1909) 

k  (1910) 

0  72 

W 

L  (1910) 

6!  74 

6:69 
0.77 
0.72 

0.73 

6!72 
0.70 

6:73 

X 

Av.    moderately 
severe  cases 

Light  diabetes. 

Case  M 

O 

0.77 

0.73 

P 

Q 

0.77 

0  75 

R 

s 

INDIRECT  CALORIMETRY. 

Although,  as  pointed  out  on  page  12,  the  direct  heat  measurement  in  this 
series  of  experiments  was  unsatisfactory  in  a  large  majority  of  the  cases,  it 
is  important  to  record  that  in  one-third  of  the  experiments  in  which  accuracy 
in  the  heat  measurements  is  assured,  the  relationships  between  the  oxygen  con- 
sumption, carbon-dioxide  production,  and  heat  production  are  essentially  those 
recorded  in  the  earlier  publication.  We  have,  therefore,  no  reason  to  change 
our  belief  that  the  calorific  equivalents  of  carbon  dioxide  and  oxygen  are  essen- 
tially as  previously  outlined,  namely,  3.26  calories  per  gram  of  carbon  dioxide 
and  3.31  calories  per  gram  of  oxygen.  If,  then,  in  experiments  with  subjects 
having  severe  diabetes,  the  carbon-dioxide  production  is  accurately  deter- 
mined, we  believe  that  the  heat  production  can  be  computed  with  considerable 
accuracy  by  multiplying  the  total  carbon-dioxide  production  in  grams  by  the 
factor  3.26. 

Usually,  since  the  carbon-dioxide  production  is  obtained  with  the  subject 
absolutely  quiet,  lying  in  bed,  it  can  be  easily  seen  that  the  results  obtained 
by  this  computation  will  represent  the  minimum  heat  production  and  not  the 
average  or  maximum  heat  production.     When  the  subject  is  sitting  up  it  has 


114  METABOLISM   IN    SEVERE   DIABETES. 

been  shown  that  there  is  essentially  an  increased  heat  production  amounting 
to  10  or  15  per  cent.^  Walking  and  all  muscular  activity,  also  the  partaking 
and  the  digestion  of  food,  produce  an  increase  in  the  heat  production.  The 
difference  in  heat  production  measured  on  the  same  subject  in  the  chair  calori- 
meter and  in  the  bed  calorimeter  is  further  evidence  of  the  difference  in  energy 
output.  A  careful  record  of  daily  routine,  muscular  activity,  exposure  to  cold, 
etc.,  would  be  necessary  for  the  intelligent  computation  of  the  total  output  of 
energy  from  the  carbon-dioxide  production.  It  is  not  outside  the  range  of  pos- 
sibilities that  this  factor  may  be  of  actual  benefit  in  making  a  tentative  compu- 
tation of  the  energy  requirement  in  diabetes.  That  this  carbon-dioxide  pro- 
duction can  be  determined  equally  as  well  by  the  small  respiration  apparatus 
as  with  the  large  respiration  calorimeter  has,  we  think,  been  fairly  demon- 
strated, and  we  may  conclude  from  this  research  that,  although  calorimetric 
measurements  are  highly  important  and  desirable  if  possible,  in  severe  dia- 
betes a  measurement  of  the  carbon-dioxide  production  alone,  or  still  better 
a  measure  of  the  oxygen  consumption,  will  give  the  means  for  computing 
with  great  accuracy  the  heat  production  of  the  individual  while  lying  quietly 
at  rest. 

COMPOSITION  OF  THE  ALVEOLAR  AIR  OF  DIABETICS. 

The  carbon-dioxide  tension  of  the  alveolar  air  has  come  to  be  regarded  as 
an  excellent  index  of  the  degree  of  acidosis  by  reason  of  the  interesting  obser- 
vations of  Beddard,  Pembrey  and  Spriggs"  and  the  confirmatory  work  of 
Porges,  Leimdorfer  and  Markovici.^  The  presence  of  acids  in  the  blood  causes 
the  respirator}^  center  to  respond  to  a  smaller  tension  of  carbon  dioxide  in  the 
blood ;  as  the  carbon-dioxide  tension  in  the  alveolar  air  bears  a  direct  relation 
to  that  in  the  blood,  it  is  evident  that  a  low  alveolar  carbon-dioxide  tension 
indicates  an  acidosis.  The  alveolar  carbon  dioxide  in  normal  individuals  varies 
from  about  36  to  46  mm.  tension  of  mercury  as  found  by  the  Haldane  method;* 
according  to  results  obtained  by  the  Plesch  method^  it  is  about  10  to  15  per 
cent  higher. 

The  best  method  for  determining  the  alveolar  air  has  not  yet  been  thor- 
oughly established.  Both  the  Haldane  and  Plesch  methods  involve  good  gas 
analysis  technique  and  not  a  little  cooperation  on  the  part  of  the  subject. 

Alveolar  air  determinations  were  made  on  three  of  the  subjects,  N,  Q,  and 
I,  and  are  interesting  as  showing  the  presence  and  degree  of  acidosis.  The 
observations  made  wdth  Cases  N  and  Q  were  by  the  Haldane  method;  those 
with  Case  I  were  by  the  Plesch  method.  The  results  obtained  with  Case  N 
are  given  in  table  128. 

'Emmes  and  Riche,  Am.  Journ.  Physiol.,  1911,  17,  p.  406. 

^Beddard,  Pembrey  and  Spriggs,   Journ.    Physiol.,  37,  Proceedings  Physiol.  Soc,    1908, 

p.  xxxix. 
'Porges,  Leimdorfer  and  Markovici,  Zeitschr.  f.  kUn.  Med.,  1911,  73,  p.  389. 
*Haldane  and  Priestley,  Jom-n.  Physiol.,  1905,  32,  p.  225. 
^Plesch,  Zeitschr.  f.  Exp.  Pathol,  u.  Ther.,  1909,  6,  p.  380.     The  Plesch  method,  in  fact, 

gives  the  carbon-dioxide  tension  of  the  venous  blood,  but  we  have  found  that  this 

value  bears  a  proportional  relation  to  the  alveolar  air. 


DISCUSSION    OF   RESULTS   AND    GENERAL    CONCLUSIONS. 


115 


On  several  occasions  observations  were  also  made  with  this  case  of  the 
rate  of  respiration,  and  the  total  ventilation  of  the  lungs,  the  results  being 
included  in  the  table.  Two  observations  were  likewise  made  of  the  blood- 
pressure  (Riva  Rocci),  one  at  7^  SO""  a.  m.  December  12,  and  the  second  at 
7''  10""  a.  m.  December  14;  both  gave  a  result  of  90  mm.  It  will  be  seen  that 
on  December  10,  when  the  alveolar  carbon-dioxide  tension  was  lower  and  pre- 
sumably the  acidosis  greater  than  on  December  14,  there  was  also  an  increased 
ventilation  of  the  lungs.  The  respiration  rate,  however,  did  not  vary  with  the 
alveolar  air  or  with  the  ventilation  of  the  lungs. 


Table  128.— 

-Determinations  made  on  alveolar  air  vnth  Case  N. 

Date. 

Time. 

Tension  of — 

Date. 

Time. 

Tension 

of 
carbon 
dioxide. 

Ventilation 
of  lungs. 

Respi- 
ration 

Carbon 
dioxide. 

Oxygen. 

quired  for 
10  liters.! 

minute. 

1910. 

mm. 

mm. 

1910. 

Dec.  1 
Dec.  2 

After  expt.,  10''25™a.m. 
Before  expt.,  8  a.m 

' 

17.4 
16.7 
16.4 
21.1 

122.3 
123.8 
126.6 

Dec.  10 

Before  expt.: 

7''  20™  a.m. 
7    30    a.m. 

mm. 

[18.6 
\18.9 

sees. 
73 

i9 

After  expt..  Hills'"  a.m. 

22.1 
21.7 

119.2 

7   31    a.m. 

76 
73 

19 
18 

Dec.  3 

Before  expt.,  7''  15">a.m. 
After  expt.,  10'»30™a.m. 

25.6 
25.3 

27.2 
26.8 

iis^a 

After  expt.: 

lO**  50™  a.m. 

/18.9 
\17.3 

'75 

22 

Dec.  5 

Before  expt.,  7*^  20™  a.m 

22.2 
24.2 

122.0 
117.7 

11    01    a.m. 

68 
76 

22 
22 

Dec.  7 

After  expt.,  10^  45"  a.m. 
Before  expt.,  7*'  15™  a.m. 

23.5 
24.1 
19.7 
18.3 

122.4 
120.1 

Dec.  12 

Before  expt.: 
7''  15™  a.m. 
7    22    a.m. 

/28.5 
\26.9 

iii 

i9 

After  expt..  lO^^W^a.m. 

22.1 
21.1 

7    26    a.m. 

119 
117 

18 
16 

After  expt.: 

10*^  50™  a.m. 

/28.9 
\28.9 

11    00    a.m. 

i05 

22 

11    01    a.m. 

121 

23 

11    02    a.m. 

2  75 

21 

22 

11    05    a.m. 

19 

Dec.  14 

Before  expt.: 

7    15    a.m. 
7    25    a.m. 

After  expt.: 

10'^  40™  a.m. 

10    51    a.m. 
10    54    a.m. 

/24.9 
\25.4 

/26.9 
\26.1 

169 
112 

i26 

141 

264 

ie 

18 

is 

14 

'At  room  temperature  and  observed  barometric  pressure.  *Time  required  for  5  liters. 

On  each  of  the  four  experimental  days  with  Case  Q,  the  carbon-dioxide 
tension  of  the  alveolar  air  was  determined  after  the  respiration  experiments. 
The  results  are  given  in  table  129.  On  November  19  the  subject  had  taken  no 
breakfast  previous  to  the  experiment,  but  the  two  experiments  on  November 
21  and  22  followed  an  oatmeal  breakfast,  while  that  on  November  23,  although 
the  subject  was  without  breakfast,  followed  two  oatmeal  days.  It  is  interest- 
ing to  note  that  the  carbon-dioxide  tension  is  very  much  lower  on  the  19th  than 
it  is  on  the  23d,  indicating  a  greater  acidosis  on  the  former  day;  the  experi- 
mental evidence  also  shows  that  the  metabolism  was  considerably  higher  on 


116 


METABOLISM   IN   SEVERE   DIABETES. 


the  19th  than  it  was  on  the  23d  after  the  two  oatmeal  days.  Further  reference 
will  be  made  to  these  two  days  in  the  discussion  of  the  question  of  the  relation- 
ship between  the  acidosis  and  the  severity  of  the  diabetes  and  intensity  of  the 
metabolism. 

Table  129. — Determinations  made  on  alveolar  air  iHth  Case  Q. 


Date. 

Carbo- 

Diet  previous  to       :S?*^^ 
experiment.           ^^^^^ 

1   ceding. 

Tension  of— 

Time. 

Carbon 
dioxide. 

Oxygen. 

1910. 
Nov.  19 

Nov.  21 

Nov.  22 

Nov.  23 

1 

1      gms. 
Without  breakfast...         55 

Oatmeal  breakfast. . .         55 

Oatmeal  breakfast.. .       165 

Without    breakfast,        165 
following    2    oat- 
meal days.               1 

After  experiment 

After  experiment 

After  experiment 

After  experi  ment 1 

mm. 
30.6 
32.9 
34,6 
29.5 
35.8 
.39.7 
40.3 
40,2 

mm. 

108,7 

■94^7 

During  the  short  sojourn  of  Case  I  at  the  hospital  in  February  1912,  when 
he  was  in  a  very  critical  condition  and  coma  was  impending,  a  number  of  obser- 
vations were  made  on  the  carbon-dioxide  tension  of  the  alveolar  air  in  which 
the  subject  breathed  the  same  air  several  times  in  and  out  of  a  rubber  bag.  In 
these  experiments  the  subject  first  inspired  600  c.c.  of  air,  breathing  it  back 
Table  130. — Determinations  made  on  alveolar  air  icith  Case  I. 


Date  and  time. 

Tension 
of  carbon 
dioxide. 

Pulse  per 
minute. 

Respira- 
tion per 
minute. 

Remarks. 

mm. 

Feb.  14,  1912: 

Impending  coma. 

lll-OT^a.m 

29.1 

11    15    a.m 

25.6 

18 

11    30    a.m  

27.1 

110 

11    40    a.m 

27.3 

After  taking  sodium  citrate.     Very  little  could  be  taken 
because  of  diarrhea  resulting  from  it. 

11    47    a.m 

18 

Respirations  heard  and  counted  from  across  room. 

2    34    p.m 

ii4 

Still  impending  coma.     Had  been  up  in  a  wheel  chair 
for  a  few  moments  at  noon. 

2    39    p.m 

24.8 

2    50    p.m 

io 

2    53    p.m 

26,5 

Drew  in  some  air  around  mouth  while  in.spiring. 

2    58    p.m 

26.3 

Between  12  noon  of  Feb.  14  and  7  a.m.  Feb.  15,  the  sub- 
ject took  90  grams  of  levulose.     Still  conscious;  was 
very  restless  during  the  night. 

Feb.  15,  1912: 

8^  03°  a.m 

19 

8    10    a.m 

21.6 

8    20    a.m 

17.5 

8    35    a.m 

22.4 

" 

Took  some  sodium  citrate  at  8**  30™  a.m.;  none  previous 
since  2*'  30™  a.m. 

8   47    a.m 

118 

8    48    a.m 

21.4 

9    00    a.m 

m.6 

21 

Dressed,  readv  to  go  home.     Still  breathing  heavily; 

5    00  p.  m.  about 

[19.5 

probably  no  better. 
Had  had  morphine  in  afternoon. 

and  forth  four  times  in  20  seconds.  The  last  expiration  was  analyzed  for  carbon 
dioxide.  The  values  obtained  are  given  in  table  130,  together  with  a  few 
records  of  the  pulse  and  respiration  rates. 

This  subject  was  characterized  by  an  abnormally  high  pulse-rate  running 
from  110  to  118;  although  the  respiration-rate  was  not  extraordinarily  high, 


DISCUSSION    OF   RESULTS   AND    GENERAL    CONCLUSIONS.  117 

averaging  not  far  from  19  per  minute,  the  deep  breathing  of  impending  coma 
was  very  noticeable,  the  respirations  being  easily  counted  from  across  the  room 
with  one's  back  to  the  subject.  A  gradual  fall  in  the  carbon-dioxide  tension 
will  be  noticed  during  the  two  days  on  which  experiments  were  made.  Between 
noon  of  February  14  and  7  a.  m.  of  February  15  the  subject  took  90  grams  of 
levulose,  but  this  seems  to  have  had  no  effect  on  the  carbon-dioxide  tension  in 
the  alveolar  air. 

Comparison  of  the  Metabolism  of  Diabetics  with  that  of 
Normal  Individuals. 

One  of  the  difficulties  hitherto  encountered  in  the  interpretation  of  experi- 
ments on  the  metabolism  of  diabetic  patients  has  been  the  lack  of  sufficient 
controls  with  normal  individuals.  In  our  previous  report  we  were  able  in  a 
measure  to  supply  this  deficiency,  and,  we  believe,  presented  enough  data 
regarding  normal  individuals  to  establish  a  satisfactory  base-line  for  com- 
parison. Criticism,  however,  has  arisen  not  only  as  to  the  character  of  the 
normals  selected,  but  also  as  to  the  number.  Lusk,^  whose  opinion  on  matters 
of  diabetes  is  not  to  be  regarded  lightly,  maintained  that  the  normal  individuals 
weighed  very  much  more  than  did  the  diabetics  and  hence  were  not  comparable 
on  the  basis  of  per  kilogram  of  body-weight.  In  the  second  place,  Lusk  laid  a 
great  deal  of  stress  upon  the  fact  that  one  of  the  subjects.  Case  I,  was  extremely 
high-strung,  nervous,  and  apprehensive,  and  by  no  means  an  ideal  subject.  He 
maintained  that  the  results  with  this  individual  played  too  important  a  role  in 
our  determination  of  the  apparent  increase  in  metabolism.  Leaving  out  of 
consideration  the  heavy  individuals  used  in  the  normal  comparison,  and  omit- 
ting, also,  the  results  obtained  with  Case  I,  he  computed  that  the  increase  in 
the  heat  production  was  but  5  per  cent  instead  of  the  15  per  cent  that  we 
maintained. 

At  the  time  of  going  to  press  with  the  first  diabetic  pubUcation,  the  num- 
ber of  normal  individuals  available  for  comparison  was  somewhat  limited,  and 
it  was  obviously  desirable  to  increase  this  as  rapidly  as  possible.  Fortunately 
in  the  intervening  time  we  have  been  able  to  study  a  sufficiently  large  number 
of  normal  individuals  so  as  to  extend  the  list,  and  are  now  prepared  to  meet 
this  criticism  by  presenting  data  based  on  (1)  an  enlarged  number  of  normal 
subjects,  and  (2)  a  normal  individual  corresponding  in  height  and  weight  for  all 
of  the  diabetics  save  one.  We  also  have  normals  to  correspond  with  two  dia- 
betics during  the  several  stages  of  their  disease  when  their  weight  changed. 
While,  therefore,  in  the  first  report  the  comparisons  were  made  between 
normal  individuals  collectively  and  diabetic  individuals  collectively,  we  shall 
attempt  in  this  publication  to  compare  each  diabetic  with  one  or  more  normal 
individuals  with  essentially  the  same  body-weight  and  height,  and  finally,  as 
before,  to  compare  normals  and  diabetics  collectively.  Under  these  conditions 
the  criticism  of  Professor  Lusk  can  be  much  better  met  than  it  could  have  been 
two  years  ago,  when  the  normal  data  were  limited.     That  Professor  Lusk's 

'Lusk,  loc.  cit. 


118  METABOLISM   IN   SEVERE   DIABETES. 

criticism  was  more  of  a  theoretical  than  a  practical  nature  is  demonstrated  by 
the  fact  that  the  actual  increase  in  metabolism  noted  in  the  new  observations 
is  somewhat  higher  than  that  noted  when  the  earlier  tests  were  made. 

The  measurements  of  the  metabolism  of  Case  I  were  stated  in  the  first 
report  to  be  unsatisfactory  for  the  reason  that  the  subject  was  high-strung  and 
nervous,  and  consequently  by  no  means  an  ideal  subject.  Fortunately,  some 
months  later  it  was  possible  to  secure  this  subject  for  another  experiment. 
At  this  time  he  was  weak,  emaciated,  and  disinclined  to  muscular  activity. 
During  the  experimental  period  he  lay  in  the  bed  calorimeter  extremely  quiet, 
and  prior  to  the  experiment  exhibited  none  of  the  nervousness  and  excitement 
which  he  had  shown  before  the  two  experiments  of  the  year  previous.  These 
later  results  may  accordingly  be  taken  as  a  measurement  of  the  metabolism 
of  a  diabetic  with  severe  acidosis,  but  with  a  minimum  amount  of  extraneous 
muscular  activity.  While,  therefore,  in  the  earlier  experiments  with  the  chair 
calorimeter  he  did  not  appear  to  be  an  ideal  subject,  in  his  last  experiment  with 
the  bed  calorimeter  no  criticism  could  be  raised  with  regard  to  the  conduct  of 
the  experiment  or  to  the  subject  himself,  so  that  the  influence  of  extraneous 
muscular  activity  may  be  disregarded.  The  results  of  the  last  experiment  with 
the  subject  abundantly  confirm  those  of  the  first  two  in  showing  a  marked 
increase  in  the  total  metabolism. 

SELECTION  OF  CONTROLS. 

In  this  comparison  of  normal  individuals  with  diabetics  care  has  been  taken 
to  select  controls  that  approximate  as  nearly  as  possible  the  exact  body- weight 
and  height  of  the  diabetic  subjects  to  which  they  are  to  be  compared.  This  has 
been  difficult  in  certain  instances,  owing  to  the  fact  that  frequently  the  dia- 
betics were  much  emaciated  and  it  was  difficult  to  find  a  person  of  a  correspond- 
ing height  and  weight.  The  evidence  with  regard  to  the  disproportion  between 
skin  area  and  body-weight,  first  suggested  by  Magnus-Levy  and  considered  by 
us  in  the  earlier  publication,  has  been  further  amplified  by  observations  during 
an  experiment  with  prolonged  inanition.  Although  during  this  experiment 
the  subject  lost  in  weight  15  kilograms,  there  was  no  loosening  of  the  skin. 
The  skin  contracted  as  the  flesh  disappeared  and  hence  there  was  no  evidence 
that  there  was  a  disproportion  between  the  body -surface  and  the  body-weight. 

A  further  precaution  was  taken  to  select  normal  subjects  who  were  not  on 
the  laboratory  staff,  except  when  it  was  necessary  in  order  to  obtain  subjects 
that  were  comparable  in  size  and  weight.  Of  the  20  or  more  subjects  used  for 
comparison,  more  than  half  did  not  belong  to  the  laboratory  staff;  hence,  on 
the  whole,  the  normal  subjects  were  more  often  untrained  than  were  the 
diabetics  with  most  of  whom  experiments  were  frequently  made. 

EVIDENCE  OF  THE  KYMOGRAPH  RECORDS. 

The  use  of  one  or  more  tube  pneumographs  about  the  thighs  or  chest  for  a 
record  of  the  degree  of  muscular  activity  of  the  subject  has  proved  a  most  suc- 
cessful venture,  but  the  expense  incidental  to  reproducing  kymograph  records 
makes  it  impossible  to  present  them  here.     A  most  careful  scrutiny  of  the 


DISCUSSION    OF   RESULTS   AND    GENERAL    CONCLUSIONS.  119 

large  number  of  kymograph  records  obtained  in  connection  with  this  research 
makes  it  evident  that  the  normal  individuals  on  the  whole  were  considerably- 
more  restless  than  were  the  diabetic  individuals.  The  diabetic  patients  were 
for  the  most  part  sick,  v/eak,  and  disinclined  to  any  extraneous  muscular  move- 
ments and  remained  lying  quietly  in  bed.  It  may  therefore  be  safely  stated 
that  the  influence  of  extraneous  muscular  activity  was  infinitely  less  Avith  the 
diabetics  than  with  the  normal  individuals.  Hence  one  would  expect  to  find 
a  higher  metabolism  with  the  normal  individuals  than  with  the  diabetics,  as 
the  influence  of  even  minor  muscular  activity  upon  the  metabolism  is  surpris- 
ing— a  fact  only  appreciated  by  one  who  is  constantly  working  in  the  labora- 
tory, measuring  the  metabolism  of  a  subject  and  comparing  the  simultaneous 
records  of  muscular  activity.  This  relationship  between  minor  muscular  activ- 
ity and  metabolism  has  been  observed  in  this  laboratory,^  even  with  infants. 

In  an  experiment  designed  to  answer  a  criticism  as  to  the  soundness  of 
using  kymograph  records  to  indicate  muscular  rest,  it  was  found  by  actual  test 
that  the  kymographs  are  so  sensitive  that  even  a  minute  muscular  tremor, 
such  as  the  movement  incidental  to  slight  shivering,  is  instantly  transmitted 
to  the  tambour  and  recorded  on  the  kymograph. 

DETAILED  COMPARISON  OF  NORMALS  AND  DIABETICS. 

From  our  list  of  normal  subjects  it  is  possible  to  select  for  purposes  of  com- 
parison one  or  more  to  compare  with  each  individual  diabetic,  with  the  single 
exception  of  Case  N.  As  he  was  a  boy,  we  had  no  normal  subject  who  was 
comparable  in  age,  weight,  and  height;  consequently.  Case  N  is  not  included  in 
the  averages.  On  one  occasion  Case  A  weighed  51.6  kilos.,  and  later  weighed 
46.1  kilos.;  a  fall  in  body-weight  of  7  kilos,  was  likewise  noticed  with  Case  C. 
Accordingly,  in  order  to  make  the  analogy  as  complete  as  possible,  we  have 
compared  the  diabetics  with  different  normals  at  the  stages  of  the  disease  when 
there  was  a  change  in  their  body-weights.  All  these  comparisons  have  been 
brought  together  in  table  131,  in  which  are  grouped  first,  the  cases  of  severe 
diabetes  and  the  normal  individuals  with  whom  they  are  compared,  and  second, 
the  moderately  severe  and  light  cases,  of  which  only  three  were  studied.  Of 
particular  interest  are  the  comparisons  between  the  cases  of  severe  diabetes 
and  the  normal  individuals. 

The  carbon-dioxide  production  per  kilogram  of  body-weight  with  all  of  the 
cases  of  severe  diabetes  was  3.31  c.c.  per  kilogram  per  minute,  and  with  normal 
individuals  3.13  c.c.  per  kilogram  per  minute.  This  increase,  which  is  approxi- 
mately but  6  per  cent,  is  fully  in  line  with  that  noted  in  the  earlier  publication, 
and  is  obviously  explained  in  part  by  the  fact  that  the  metabolism  of  the  diabe- 
tics was  essentially  a  protein-fat  metaboHsm,  while  that  of  the  normal  subjects 
was  unquestionably  a  protein-fat  and  glycogen  or  carbohydrate  metabolism. 

As  pointed  out  earlier,  the  difference  between  the  carbon-dioxide  produc- 
tion on  these  two  groups  of  individuals  does  not  measure  by  any  means  the 
difference  in  the  actual  metabolism.   This  is  best  shown  by  a  comparison  of  the 

'Benedict  and  Talbot,  Am.  Journ.  Diseases  of  Children,  1912,  3,  p.  1. 


120 


METABOLISM   IN    SEVERE   DIABETES. 


oxygen  consumption.     Of  the  19  severe  cases,  the  intensity  of  the  metaboUsm 

as  measured  by  the  oxygen  consumption  was  in  each  individual  case  higher 

than  that  of  the  normal  individuals  with  whom  they  are  compared.     The 

single  exception  was  Case  B,  the  normal  individual,  Miss  E.  W.,  having  the 

Table  131.— Comparison  of  the  carbon  dioxide  eliminated  and  oxygen  absorbed  by 
diabetics  and  normal  individuals  in  experiments  without  food. 

[Bed  calorimeter  and  respiration  apparatus.] 
SEVERE  DIABETES. 


Diabetic. 

Normal. 

Subject. 

■Si 

•53  _o 

•0 

Si 

11 

-A 
0 

0^ 

0 

Subject. 

J3 

h 

■So 
?~ 

^° 
pq 

.a 

bO 

■« 
W 

"o 
II 

0 

1. 

.11 
oE 
-0  t- 

II 

0 

l| 

X 

0 

Case  A 

Mlos 
51.6 
46.1 
41.4 

62.7 

55.5 

48,8 
67.1 
52.4 
40.0 
52.9 
59.1 
55.6 
63.0 
66.5 

31.5 
52.6 
40.0 
51.7 

55.3 
58.0 
51.4 

39.5 
60.0 

cm. 
171 
171 
158 

166 

166 

173 
178 
159 
176 
171 
180 
180 
183 
183 

146 
173 
173 
168 

181 

177 
180 

160 
173 

1 

1 
5 

6 

7 

3 
1 
7 
1 
1 
1 
3 
1 
1 

7 
3 
5 
2 

1 
1 
2 

5 
1 

c.c. 
3.22 
2.89 
3.10 

2.81 

3.01 

3.11 
3.22 
3.09 
4.33 
3.48 
2.84 
3.31 
3.44 
3.08 

4.11 
3.06 
3.75 
3.36 

3.51 
2.64 
3.29 

3.80 
3.42 

C.C. 

4.22 
4.08 
4.29 

4.12 

4.35 

4.19 
4.38 
4.05 
6.03 
4.54 
4.04 
4.65 
4.41 
4.23 

5.57 
4.24 
5.34 
4.37 

4.90 
3.67 
4.51 

5.20 
4.72 

A.F.  G 

T.  M.  C      ..     .. 

kilos. 
53.9 
48,5 
43  3 
42,6 
40,5 
37.4 
62,2 
61,1 
55,2 
55,1 
48,5 
66,0 
52,2 
48,5 
55,1 
58,5 
57,8 
63,2 
66,7 
66.0 

cm. 
175 
166 
157 
165 
157 
155 
164 
165 
164 
169 
166 
177 
158 
166 
169 
181 
179 
185 
182 
182 

i68 
166 
162 
175 
179 
179 
179 
175 
165 
157 
155 
173 

1 

18 
3 
2 
2 
2 
31 
13 
9 
9 
18 
54 
2 
18 
9 
5 
44 
4 
16 
13 

'2 

18 

19 

1 

44 

44 

44 

1 

2 

2 

2 

7 

c.c. 
3.30 
3.25 
3.30 
3,24 
3,78 
3.26 
2,89 
2,96 
2,89 
3,14 
3,25 
3,12 
3  31 
3,25 
3,14 
2.62 
2.86 
2.71 
2.92 
3.04 

3!69 
3.25 
3.66 
3,30 
2,86 
2,86 
2.86 
3.30 
3.24 
3,78 
3,26 
3.19 

c.c. 
3.88 
3.86 
3,74 
3,99 
4.57 
3,77 
3  51 
3,62 
3,55 
3,72 
3,86 
3.68 
3,91 
3,86 
3,72 
3  34 
3,32 
3,47 
3,62 
3,63 

3^67 
3,86 
4,33 
3.88 
3.32 
3,32 
3,32 
3,88 
3,99 
4,57 
3,77 
3.84 

Case  B 

Case  C 

Miss  A.  C 

MissE.  W 

Mrs.  S.  C 

H.  H.  A 

S.  A.  R 

Dr.  P.  R 

C.  H.  H 

CaseD 

T.  M.  C 

Case  G 

MAM 

CaseH 

Miss  B 

Case  I 

T  M  C 

Case  J 

C  H   H 

CaseK 

'  Dr.  S 

Case  L 

1  H.F.T 

1  E  P.  C 

Case  N 

K.  H.  A 

J.  R 

CaseO 

52.4 
48.5 
54.3 
53.9 
57.8 
57,8 
57.8 
53.9 
42.6 
40.5 
37.4 
60.0 

CaseP 

T.  M  C 

CaseQ 

V  G 

Case  R 

A.  F.  G 

H.  F.  T 

Cases 

H  F  T 

CaseT 

H.  F.  T 

Case  U 

A.  F.  G 

Miss  A  C 

Case  V 

MissE.  W 

Mrs.S.C 

H  B.  L 

Av.  severe  cases 
except  N 

Av.  normal  subjects. 

3.31 

4.54 

3.13 

3. 75 

MODERATELY  SEVERE  AND  LIGHT  DIABETES. 

Case  M 

82.1 

59.5 
64.6 

172 

161 

170 

3 

2 
1 

2.42 

2.75 
2.82 

3.14 

3.77 
3.79 

0.  F.  M 

Prof.C 

Miss  B   W 

85,8 
83.0 
59.4 
64.0 

171 
169 
162 
171 

2 
3 

2 
6 

2.44 
2.40 
3.03 
2.89 

3.12 

2.88 
3.79 
3.72 

CaseW 

CaseX 

D  M 

Av.    moderately 
severe  and  light 
cases 

Av.  normal  subjects. 

2,66 

3.57 

2.69 

3.38 

higher  metaboUsm.  On  the  other  hand,  the  three  remaining  individuals  with 
whom  Case  B  is  compared  had  a  much  lower  metabolism,  the  average  oxygen 
consumption  for  the  four  normal  subjects  being  less  than  that  of  Case  B.  The 
average  oxygen  consumption  of  the  cases  of  severe  diabetes,  Case  N  excluded. 


DISCUSSION    OF   RESULTS   AND    GENERAL    CONCLUSIONS. 


121 


was  4.54  c.c.  per  kilogram  per  minute,  while  with  the  normal  subjects  the    \ 
average  oxygen  consumption  was  3.75  c.c.     This  corresponds  to  an  increase 
of  0.79  c.c.  per  minute  above  normal,  or  somewhat  over  20  per  cent.^ 

In  the  earher  publication  it  was  stated  that  the  increase  in  metabolism  was 
not  far  from  15  to  20  per  cent,  and  it  Avill  be  seen  that  these  figures  bear  out 
perfectly  this  conclusion.  Furthermore,  taking  into  consideration  the  inti- 
mate relationship  between  minor  muscular  activity  and  metabolism,  it  is  evi- 
dent that  these  subjects  should  have  been  under  exactly  the  same  conditions 
in  regard  to  the  muscular  activity.  An  examination  of  the  many  pneumograph 
curves  obtained  on  these  subjects  shows  that  in  these  as  in  the  earlier  experi- 
ments the  normal  individuals  were  invariably  somewhat  more  restless  than 
were  the  diabetics,  which  would  tend  to  increase  their  oxygen  consumption 
above  that  of  the  diabetics.  If  the  normals  had  shown  as  little  muscular  activity 
as  did  the  diabetics,  it  is  obvious  that  their  oxygen  consumption  woidd  have  been 
still  less  than  reported,  and  that  the  increase  due  to  the  diabetes  would  be  even  greater 
than  here  shown. 

While  the  observations  on  this  point  have  to  deal  more  particularly  with 
the  comparison  between  the  cases  of  severe  diabetes  and  normals,  it  is  of  inter- 

'RoUy  (Deutsch.  Archiv  f.  klin.  Med.,  1912,  105,  p.  494)  gives  the  following  values  for 
his  cases  of  severe  diabetes: 


Subject. 

Age. 

Weight. 

Carbon  dioxide 

per  kilo. 

per  minute. 

Oxygen 

per  kilo. 

per  minute. 

Respiratory 
quotient. 

H 

yrs. 
21 
66 
21 
30 
34 
24 
20 
21 

kilos. 
44.5 
38.8 
45.3 
40.5 
51.5 
61.2 
63.5 
57.5 

c.c. 
3.969 
3.219 
3.791 
3.344 
3.565 
3.396 
3.281 
3.146 

c.c. 
5.276 
4.046 
5.168 
4.506 
4.892 
4.708 
4.830 
4.357 

0.753 
.795 
.734 
.742 
.728 
.702 
.680 
.722 

B 

Scho 

Bo                    

Schn 

Kr 

W.  K 

U.L 

3  464 
3.13 

4.723 
3  75 

Av.  found  by  Benedict 
and  Joslin  for  normal 

Leimdorfer  (Biochem.  Ztschr.,  1912,  40,  p.  326)  reports  the  niichtern  value  for  five 
severe  cases  as  follows: 


Subject. 

Age. 

Weight. 

Height. 

Carbon  dioxide 

per  kilo. 

per  minute. 

Oxygen 

per  kilo. 

per  minute. 

Respiratory 
quotient. 

Joh.  Gr 

yrs. 
36 
28 
19 
29 
15 

kilos. 
56.8 
68 
50 
50 
45 

cm. 
172 
178 
154 
159 
165 

c.c. 
2.85 
2.75 
3.56 
3.35 
3.29 

c.c. 
4.41 
4.25 
5.57 
5.23 
4.86 

0.644 
.645 
.638 
.641 
.678 

Karl  Ki 

F.  S 

Max  G 

Agn.M 

Average 

Av.  found  by  Benedict 
and  Jcslin  for  normal 
subjects 

3  16 
3.13 

4.86 
3  75 

The  abnormally  low  quotients  found  by  Leimdorfer  with  the  Zuntz-Geppert  method 
are  strikingly  at  variance  with  those  commonly  found  by  us  using  the  respiration  apparatus 
designed  in  this  laboratory  and  by  Roily  using  a  modified  form  of  it. 


122 


METABOLISM   IN   SEVERE   DIABETES. 


est  to  note  that  the  relatively  few  light  cases  of  diabetes  show  essentially  the 
same  carbon-dioxide  production  as  the  normal  subjects,  with  a  slightly  greater 
oxygen  consumption.  This  difference  in  oxygen  consumption  may  easily  be 
explained  by  the  fact  that  the  number  of  cases  studied  was  altogether  too  few 
from  which  to  draw  deductions.  If  we  compare  the  values  for  the  severe  cases 
of  diabetes  with  those  for  the  mild  cases,  we  find  that  both  the  carbon-dioxide 
excretion  and  the  oxygen  consumption  were  materially  less  with  the  moderately 
severe  and  the  light  cases  of  diabetes  than  those  -^vdth  the  severe  cases.  As 
pointed  out  earlier,  however,  they  are  in  large  part  affected  by  the  very  low 
values  found  with  Case  M. 

Comparison  of  the  Metabolism  of  Diabetics  with  Varying 
Degrees  of  Severity. 

The  observations  made  in  our  earlier  publication  indicated  that  there  was 
a  tendency  for  the  metabolism  to  increase  pari  passu  with  the  severity  of  the 
diabetes,  but  this  inference  was  based  upon  slight  experimental  data,  the  num- 
ber of  cases  of  light  diabetes  being  very  few.  Similarly,  in  connection  with  the 
new  experiments,  we  find  a  difficulty  in  drawing  a  careful  deduction  on  this 
point,  owing  to  the  fact  that  we  still  have  so  few  observations  upon  cases  of 
light  diabetes.  A  comparison  of  the  carbon-dioxide  production  and  oxygen 
consumption  per  kilogram  of  body-weight  per  minute,  as  well  as  the  respiratory 
quotient,  with  both  severe  and  light  cases,  is,  however,  of  interest.  These  com- 
parisons are  given  in  table  132. 

Table  132. — Comparison  of  the  metabolism  of  diabetics  with  varying  degrees  of  severity. 


Degree  of  severity. 

Bed  calorimeter  or 
respiration  apparatus 
per  iiilogram  of  body- 

weigiit  per  minute. 

All  experi- 
ments with 
all  forms  of 
apparatus. 

Carbon 

dioxide 

eliminated. 

Oxygen 
absorbed. 

Respiratory 
quotient. 

c.c. 
3.33 

2.82 

c.c. 
4.54 
3.73 

0.73 
0.75 

Moderately  severe  and  light  cases 

It  is  obvious  that  with  the  severe  cases  there  was  a  greater  intensity  of 
metabolism  as  indicated  by  an  increased  carbon-dioxide  production  and  an 
increased  oxygen  consumption.  On  the  other  hand,  there  was  a  lower  respira- 
tory quotient,  indicating  a  consumption  of  fat  with  a  minimum  consumption  of 
carbohydrates;  with  the  moderately  severe  and  light  cases  there  is  a  slightly 
increased  respiratory  quotient,  corresponding  to  the  slightly  greater  carbo- 
hydrate tolerance.  A  critical  examination  of  these  figures  and  the  tables  from 
which  they  are  drawn,  namely,  tables  119  to  127,  shows  that  the  values  for  the 
moderately  severe  and  light  cases  are  enormously  affected  by  the  very  low 
values  for  both  carbon  dioxide  and  oxygen  found  with  subject  M,  who  was  dis- 
tinctly fat.  While,  therefore,  the  original  contention  may  be  made  that  in  severe 
diabetes  a  somewhat  higher  metabolism  is  shown  than  in  moderately  severe  or 


DISCUSSION    OF   RESULTS   AND    GENERAL   CONCLUSIONS.  123 

light  cases,  nevertheless  there  is  a  serious  objection  to  this  form  of  comparison 
owing  to  the  fact  that  we  have  so  few  light  cases.  If,  however,  we  examine  the 
figures  in  table  120,  we  see  that  if  Case  M  be  omitted  the  carbon-dioxide  pro- 
duction is  still  lower  with  the  two  remaining  cases  than  the  average  value  for 
the  severe  cases.  Similarly,  if  the  low  oxygen  consumption  of  Case  M  be  omitted 
in  table  123,  the  average  oxygen  consumption  with  severe  cases  is  greater  than 
with  any  of  the  moderately  severe  cases;  hence  it  seems  perfectly  justifiable 
to  state  that  the  more  severe  the  case,  the  greater  the  intensity  of  the  meta- 
bolism. Thus  the  experimental  evidence  seems  to  justify  fully  our  earlier  con- 
tention to  this  effect. 

A  Comparison  of  the  Metabolism  of  Fasting  Diabetics  under 
Varying  Conditions  as  to  the  Intensity  of  the  Acidosis. 

As  was  pointed  out  in  the  earlier  report,  there  was  a  period  in  the  history  of 
Case  A  when  he  was  apparently  in  a  much  more  serious  condition  than  at  any 
other  time.  During  this  period  the  evidence  was  clear  that  both  his  meta- 
bolism and  pulse-rate  were  considerably  higher  than  at  other  times.  This 
suggested  a  relationship  between  metabolism  and  the  degree  of  severity  of  the 
diabetes,  a  suggestion  that  was  emphasized  and  accentuated  by  the  fact  that 
the  whole  group  of  subjects  with  severe  diabetes  indicated  a  higher  metabo- 
lism than  did  those  with  light  diabetes,  although  admittedly  the  number  of 
the  latter  was  too  few  for  us  to  draw  any  definite  deductions. 

In  the  new  cases  here  reported  at  least  two  gave  indications  of  a  markedly 
different  severity  of  the  disease  within  a  very  short  period  of  time,  and  these 
fluctuations  in  severity  occurred  during  the  experimental  period  at  the  labora- 
tory. Both  cases  were  boys.  With  Case  N  it  was  noted  that  on  days  fol- 
lowing green  days  the  metabolism  was  high,  there  was  a  higher  excretion  of 
/3-oxybutyric  acid,  the  pulse-rate  was  high  and  the  alveolar  carbon-dioxide 
tension  was  low.  On  days  following  oatmeal  days,  on  the  other  hand,  the 
metabolism  was  distinctly  lower,  the  pulse-rate  lower,  and  the  alveolar  carbon- 
dioxide  tension  was  higher.  The  results  with  this  case  were,  however,  com- 
plicated by  an  uncertainty  as  to  whether  there  was  not  a  surreptitious  inges- 
tion of  food;  since  the  ingestion  of  food  per  se  would  stimulate  metabolism,  it  is 
uncertain  whether  the  high  metabolism  experienced  on  certain  dates  was  due  to 
the  severity  of  the  disease  or  to  the  previous  ingestion  of  food.  Nevertheless 
the  other  evidence,  particularly  the  carbohydrate  balance,  is  of  material  assist- 
ance in  determining  whether  or  no  food  was  ingested  prior  to  coming  to  the 
laboratory,  and  we  beUeve  that  for  the  two  days  here  cited  there  is  reasonable 
ground  for  belief  that  the  actual  conditions  of  metabolism  were  not  compli- 
cated by  the  previous  ingestion  of  food.    The  results  are  given  in  table  133. 

On  November  30  to  December  1  the  acidosis  was  severe;  the /3-oxybutyric 
acid,  which  was  fortunately  determined  on  that  day,  amounted  to  35  grams, 
with  a  minus  carbohydrate  balance  of  25  grams;  the  oxygen  consumption  was 
179  c.c.  with  a  pulse-rate  of  75  and  a  carbon-dioxide  tension  of  17  mm.  On 
December  1  the  subject  had  an  oatmeal  day,  and  on  December  2  to  3,  the  dia- 


124 


METABOLISM   IN    SEVERE   DIABETES. 


cetic  acid  reaction  and  the  carbohydrate  balance  were  essentially  the  same,  but 
there  was  a  fall  in  the  ammonia-nitrogen  nitrogen  ratio ;  there  was,  however, 
a  considerably  lower  metabolism,  inasmuch  as  but  160  c.c.  of  oxygen  were 
consumed  per  minute,  the  pulse-rate  was  57,  and  the  alveolar  carbon-dioxide 
tension  was  26  mm.  Unfortunately  the  /3-oxybutyric  acid  was  not  determined. 
In  examining  the  original  table  for  this  case  (table  33)  we  find  varying 
days, even  when  the  subject  was  supposed  to  be  fasting, the  variations  in  the 
oxygen  consumption  ranging  from  179  down  to  as  low  as  160.  These  high  days 
can  not  always  be  sharply  designated  as  being  days  on  which  no  food  was 

Table  133. — Comparison  of  the  metabolism  of  Case  N  under  varying  conditions  of  acidosis. 


Date. 

Diacetic 
acid. 

0-oxy- 

butyric 

acid. 

NH3-N 
Total  N 

Carbo- 
hydrate 
balance. 

Metabolism  at 
beginning  of 
following  day. 

Alveolar 
carbon- 
dioxide 
tension. 

Oxygen 
per  kilo- 
gram per 
minute. 

Pulse- 
rate. 

1910. 
Nov.  30-Dec.  1 

++++ 
++++ 

gms. 
35 

? 

p.  ct. 

42 
36 

gms. 
-25 
-15 

c.c. 
179 
160 

75 
57 

Tnm, 
17 
26 

Dec.  2-3 

taken,  as  we  have  reason  to  believe  that  the  subject  took  food  on  one  or  two 
occasions  before  coming  to  the  laboratory,  either  through  a  misunderstanding 
or  otherwise,  and  it  was  not  properly  reported.  In  any  event,  the  relationship 
between  the  intensity  of  the  metabolism,  the  diet  of  the  previous  day,  and  the 
general  physical  condition  of  the  subject  was  such  as  to  be  of  considerable 
significance,  and  seemed  to  indicate  a  rather  close  connection  between  the 
severity  of  the  acidosis  and  the  intensity  of  metabolism. 

With  Case  Q  we  are  confident  that  the  diet  was  properly  controlled.  We 
have  accordingly  selected  two  days  with  this  subject  in  which  both  the  degree 
of  acidosis  and  the  total  metabolism  were  determined.  The  results  are  given 
in  table  134.  Under  these  conditions  we  find  on  November  18-19,  when  there 
was  severe  acidosis  with  a  large  amount  of  /3-oxybutyric  acid  and  a  low  carbo- 
hydrate balance,  that  the  metabolism  and  pulse-rate  were  considerably  higher 
than  three  days  later,  when  the  /3-oxybutyric  acid  was  two-thirds  that  of  the 
first  and  the  positive  carbohydrate  balance  was  considerable,  this  day  being  a 
carbohydrate  oatmeal  day.  There  was  likewise  an  increase  in  the  tension  of 
the  alveolar  carbon  dioxide.  On  the  other  hand,  the  whole  comparison  is  some- 
what complicated  by  the  fact  that  the  volume  of  urine  on  the  second  day  was 
but  one-half  that  of  the  first  day ;  the  total  amount  of  nitrogen  was  also  lower. 
This  of  course  would  keep  up  the  high  percentage  of  ammonia  nitrogen,  and 
might  account  for  the  low  excretion  of  j8-oxybutyric  acid,  but  need  not  neces- 
sarily affect  the  carbohydrate  balance.  It  is  much  to  be  regretted  that  other 
experiments  without  food  could  not  have  been  made  with  this  subject,  but  the 
only  other  two  experiments  obtained  with  him  were  after  definite  feeding. 

The  results  of  the  experiments  with  Cases  N  and  Q  strongly  suggest  an 
intimate  relationship  between  the  severity  of  diabetes  and  high  metabohsm; 


DISCUSSION    OF   RESULTS   AND   GENERAL   CONCLUSIONS. 


125 


while  this  evidence  from  experiments  with  individual  subjects  is  by  no  means 
conclusive,  it  supplements  the  general  impression  derived  from  experiments 
with  different  individuals  that  with  severe  diabetes  there  is  a  high  metabolism, 
and  with  mild  diabetes  a  lower  metabohsm.  This  last  inference,  however,  is 
drawn  from  experiments  with  different  individuals,  while  the  experiments  with 
Cases  N  and  Q  imply  that  with  the  same  individual,  differences  in  intensity 
of  the  disease  may  be  accompanied  by  differences  in  the  intensity  of  the 
metabolism  as  measured  by  the  oxygen  consumption,  the  pulse-rate,  and  the 
alteration  in  the  carbon-dioxide  tension  of  the  alveolar  air. 

Table  134. — Comparison  of  the  metabolism  of  Case  Q  under  varying  conditions  of  acidosis. 


Date. 

Diacetic 
acid. 

/3-oxy- 

butyric 

acid. 

NH3-N 
Total  N 

Carbo- 
hydrate 
balance. 

Metabolism  at 

beginning  of 
following  day. 

Alveolar 
carbon- 
dioxide 
tension. 

Oxygen 
per  kilo- 
gram per 
minute. 

Pulse- 
rate. 

79 
65 

1910. 
Nov.  18-19 

+++ 
++++ 

gms. 

30 

19.6 

p.  ct. 
27.4 
25.9 

gms. 
-55 

+75 

c.c. 
232 
220 

mm. 
31 

40 

Nov.  22-23 

The  Influence  of  a  Normally  Induced  Acidosis  upon  Metabolism. 

Since  diabetics  with  severe  acidosis  showed  a  higher  metabolism  than  did 
light  cases,  and  since  the  metabolism  was  higher  with  the  same  individual  when 
the  diabetes  was  very  severe  than  when  it  was  milder,  it  seemed  desirable  to 
find  out  the  effect  of  an  experimentally  induced  acidosis  upon  the  metabolism 
of  normal  individuals.  While  studying  in  the  laboratory  of  Dr.  Joseph  Barcroft, 
of  Cambridge,  England,  Mr.  H.  L.  Higgins,  an  associate  in  this  laboratory, 
made  some  interesting  observations  on  the  relationship  between  the  effect  of 
a  carbohydrate-free  diet  and  the  dissociation  curve  of  the  blood.  While  upon 
a  carbohydrate-free  diet  he  observed  great  lassitude  and  a  general  feeling  of 
malaise.  On  repeating  this  experiment  in  the  fall  of  1911,  it  occurred  to  him 
that  a  study  of  the  metabolism  as  measured  by  the  oxygen  consumption  and 
carbon-dioxide  production  during  this  period  would  be  of  interest,  and  hence 
some  observations  were  made  of  the  total  metabolism.  Subsequently,  a 
second  experiment  was  made  with  another  subject,  H.  H.  A.,  a  student  in  the 
Harvard  Medical  School.  This  was  more  carefully  planned,  with  the  special 
purpose  of  studying  the  effect  of  the  carbohydrate-free  diet  upon  the  meta- 
bolism. 

In  a  paper  recently  published  by  Benedict  and  Higgins,^  discussing  the 
effect  of  the  amount  of  carbohydrates  in  the  preceding  diet  upon  the  respira- 
tory quotient,  it  was  shown  that  the  respiratory  quotient  with  a  carbohydrate- 
free  diet  was  as  low  as  the  ordinary  quotients  in  diabetes,  if  not  lower,  and  that 
the  respiratory  quotient  could  be  elevated  persistently  by  increasing  the  quan- 


'Benedict  and  Higgins,  Am.  Journ.  Physiol.,  1912,  30,  p.  217. 


126  METABOLISM   IN   SEVERE   DIABETES. 

tity  of  carbohydrates  in  the  diet.  Inasmuch  as  this  paper  dealt  especially 
with  the  character  and  not  wdth  the  amount  of  the  metabolism,  practically  no 
reference  was  made  to  the  significant  fact  that  apparently  the  lower  the  amount 
of  carbohydrates  in  the  diet,  the  higher  the  metabolism.  It  is  the  purpose  of 
the  following  section  of  this  discussion  to  state  the  details  of  these  experiments 
and  to  discuss  the  results. 

EXPERIMENTS  WITH  H.  L.  H. 

The  study  made  with  this  subject  included  four  experiments,  all  with  the 
respiration  apparatus.  Three  of  these  were  made  with  the  carbohydrate-free 
diet;  the  fourth  followed  normal  diet.  The  special  diet  was  begun  on  Sep- 
tember 6,  1911,  but  the  plan  to  study  the  respiratory  exchange  was  not  devel- 
oped until  the  next  day,  so  that  the  first  respiration  experiment  was  made  on 
September  7,  1911.  The  experiment  on  normal  diet  was  therefore  delayed 
until  the  second  day  after  the  discontinuance  of  the  carbohydrate-free  diet. 
The  vital  statistics  for  this  subject  are  as  follows: 

Date  of  birth,  March  26, 1887;  height,  172  centimeters;  body- weight  with- 
out clothing  during  experiments,  60.2  kilos. 

STATISTICS   OF  EXPERIMENTS  WITH  H.  L.  H. 

Respiration  Experiment  No.  1. 

Date,  September  7,  1911.     Body- weight  without  clothing,  60.2  kilos. 

The  last  meal  preceding  the  beginning  of  the  carbohydrate-free  diet  was 
taken  at  12''  30™  p.  m.,  September  5,  and  consisted  of  beef  stew  with  vegetables 
and  bread  and  butter.  The  subject  fasted  the  remainder  of  the  day.  On  the 
day  preceding  the  first  experiment  he  took  for  his  breakfast  eggs  and  beef  tea; 
for  dinner,  sardines  and  cheese;  and  for  supper,  pork  chops.  Samples  of  the 
alveolar  air  were  taken  at  2^  56""  and  3''  52"°  p.  m.  on  this  day. 

On  the  experimental  day  the  subject  came  to  the  laboratory  fasting;  the 
experiment  began  at  S^  SO""  a.  m.,  continued  for  three  15-minute  periods,  with 
intermissions  of  19  and  11  minutes  respectively,  and  ended  at  9^  55™  a.  m. 
The  pulse-rate  ranged  from  80  to  88.  The  results  of  the  experiment  are  given 
in  table  135.  After  the  experiment  was  over  the  subject  ate  for  his  breakfast 
at  10  a.  m.  soft-boiled  eggs  mth  butter;  also  took  pepsin  gum.  For  his  dinner, 
at  Z^  30"  p.  m.,  he  again  took  soft-boiled  eggs  with  butter,  while  for  his  supper 
he  ate  fried  ham  with  a  little  butter. 

Respiration  Experiment  No.  2. 

Date,  September  8,  1911.  Body-weight  without  clothing,  60.2  kilos, 
(assumed) . 

At  8  a.  m.  on  the  experimental  day  the  subject  took  a  few  sips  of  coffee,  a 
piece  of  pepsin  gum,  and  a  little  lemon  juice.  The  experiment  began  at  9^  25™ 
a.  m.,  continued  for  three  15-minute  periods  with  intermissions  of  11  and  9 
minutes  each,  and  ended  at  lO'^  30™  a.  m.  The  pulse-rate  ranged  from  72  to 
80.  The  food  taken  by  the  subject  throughout  the  day  consisted  of  a  break- 
fast of  lamb  chops  at  lO''  30™  a.  m.,  a  dinner  of  sardines  at  2^  30™  p.  m.,  and  a 
supper  of  beefsteak  at  8  p.  m..  Samples  of  the  alveolar  air  were  taken  on  this 
day.    The  results  of  the  experiment  are  given  in  table  135. 


DISCUSSION    OF   RESULTS   AND    GENERAL   CONCLUSIONS. 


127 


Respiration  Experiment  No.  3. 

Date,  September  9,  1911.  Body-weight  without  clothing,  60.2  kilos. 
(assumed). 

This  experiment  began  at  9^  SS""  a.  m.  with  the  subject  fasting,  was  con- 
tinued for  two  15-minute  periods,  and  ended  at  10''  SI""  a.  m.  The  pulse-rate 
ranged  from  64  to  78.  The  carbohydrate-free  diet  was  discontinued  beginning 
with  this  day,  no  record  being  made  of  the  food  eaten  on  this  and  succeeding 
days.     The  results  of  the  experiment  may  be  found  in  table  135. 

RespirationTExperiment  No.  4. 

Date,  September  11,  1911.  Body-weight  without  clothing,  60.2  kilos, 
(assumed). 

On  the  second  day  after  the  discontinuance  of  the  carbohydrate-free  diet, 
another  respiration  experiment  was  made  with  the  subject  after  a  12-hour  fast. 
The  experiment  began  at  S^  22°^  a.  m.,  continued  for  three  15-minute  periods, 
and  ended  at  O'^  37°^  a.  m.  The  pulse-rate  ranged  from  66  to  72.  The  results 
of  the  experiment  are  given  in  table  135. 


Table  135.- 

-Results  of  respiration  experiments  Nos.  1  to  4  with  H.  L 

.  H.,  without  food. 

Experi- 
ment 
No. 

Date. 

Diet  and  time. 

Duration. 

Carbon 

dioxide 

eliminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 
respiration- 
rate. 

1 

2 
3 

4 

1911. 
Sept.  7 . . 

Sept.  8 . . 

Sept.  9 . . 

Sept.  11. 

Carbohydrate  free.^ 

S""  50"  a.m 

9    14    a.m 

9    40    a.m 

Average 

9"  25"  a.m 

9    51    a.m 

10    15    a.m 

Average 

9'' .53"  a.m 

10    16    a.m 

Average 

Normal.^ 

S^^  22"  a.m 

8  50    a.m 

9  21    a.m 

Average 

min.   sec. 
15      4 
IS      7 
15     10 

is     7 

15      4 
15      6 

is   '9 

15      4 

15    24 
15    40 
15    18 

c.c. 
206 
197 
198 
200 
209 
196 
189 
198 
198 
191 
195 

212 
207 
211 
210 

c.c. 
305 
292 
301 
299 
281 
279 
280 
280 
276 
268 
272 

248 
233 
248 
243 

0.68 
.67 
.66 
.67 
.75 
.70 
.68 
.71 
.72 
.71 
.72 

.86 
.89 
.85 
.87 

85 
83 
84 
84 
76 
75 
74 
75 
70 
74 
72 

69 
67 
71 
69 

16 
15 
16 
16 
16 
17 
16 
16 
16 
16 
18 

16 
17 
15 
16 

'Subject  began  the  carbohydrate-free  diet  after  the  noon  meal  of  Sept.  5,  1911. 
2  Subject  resumed  his  normal  diet  on  the  morning  of  Sept.  9,  1911. 

RESULTS   OF   EXPERIMENTS   WITH   H.    L.    H. 

It  is  obvious  from  the  data  given  in  table  135  for  the  oxygen  consumption 
that  the  metabolism  was  much  higher  during  the  carbohydrate-free  diet  than 
during  the  normal  diet.  This  is  further  substantiated  by  the  fact  that  the 
pulse-rate  was  higher,  particularly  on  the  first  day  on  which  measurements 
were  secured. 

Table  136. — Statistics  of  urine — Subject  H.  L.  H. 


Date. 

Period. 

Volume 
of  urine. 

Acetone. 

(3-oxy- 

butyric 

acid. 

Nitrogen. 

Ammonia. 

T,  .„,      NHj-N 
^°*^'-     Total  N' 

1911. 
Sept.  6-71.. 
7-8.. 
8-9... 

8*^  45"  a  m.  to  ^^  25"  a.m 

c.c. 
1130 
1120 
1300 

gms. 
1.548 
1.726 
2.792 

gms. 
4.247 

gms. 
21  92 
18.05 
18.93 

gms.         p.  ct. 
1.58            5.9 
2.46           11.2 
4.07           17.7 

8    25    a.m.       7    50    a.m  

7    50    a  m.       9    35    a.m 

•The  subject  subsisted  on  a  carbohydrate-free  diet  after  the  noon  meal  of  Sept.  5,  1911. 


128 


METABOLISM   IN   SEVERE   DIABETES. 


Urine  analyses. — To  study  the  degree  of  acidosis,  the  subject  made  a  care- 
ful urine  analysis  on  three  days  of  the  study.  The  results  of  these  analyses  are 
reported  in  table  136.  Unfortunately,  the  value  for  /3-oxybutyric  acid  on  Sep- 
tember 7-8  is  questionable  and  is  therefore  not  included.  It  will  be  seen  that 
there  was  a  measurable  amount  of  acetone  and  jS-oxybutyric  acid  appearing  in 
the  urine;  there  was  also  an  increase  in  the  amount  of  ammonia  which  rose 
on  the  last  day  to  about  4  grams  with  approximately  18  per  cent  of  the 
total  nitrogen  in  the  form  of  ammonia-nitrogen.  These  commonly  accepted 
indices  of  an  acidosis  are  particularly  well  shown  in  this  experiment. 

Composition  of  the  alveolar  air. — This  subject  had  been  particularly 
interested  in  studying  the  composition  of  alveolar  air  and  so  made  a 
number  of  observations  upon  himself  prior  to  and  during  the  experiment,  the 
results  of  which  are  given  in  table  137.  Of  special  interest  is  the  carbon- 
dioxide  tension,  which  falls  below  the  normal  immediately  after  the  beginning 
of  the  carbohydrate-free  diet,  the  average  on  September  8  being  some  7  mm. 
below  the  normal.     The  oxygen  consumption  shows  a  corresponding  increase. 

Table  137. — Determinations  made  on  alveolar  air  with  H.  L.  H. 


'  Carbon- 
Date  and  time.         1    dioxide 
i   tension. 

1 

Oxygen                   q-  . 
tension.                   ^'^*- 

1911. 
July  21-22,  average 

mm. 
36.5 

mm. 
111.1 

Normal. 

Carbohydrate-free. ' 
Carbohydrate-free. 

Sept.  6: 

2''56™p.m 

3    52    p.m 

35.5 
33.9 

103.8 

Sept.  8  - 

29.9 
28.6 
30.3 

120.4 

Average 

29.6 

120.4 

'Subject  beean  the  carbohvdrate-free  diet  after  the  noon  meal  of 

Sept.  5,  1911.     He  ate  food  at  12*'  20°'  p.m.  Sept.  6. 
'Probably  after  food. 

EXPERIMENTS  WITH  H.  H.  A. 

The  important  point  observed  in  connection  with  the  study  with  H.  L.  H., 
namel}',  an  increased  metabolism  incidental  to  the  ingestion  of  a  carbohydrate- 
free  diet,  justified  a  second  carefully-planned  study  on  another  subject.  The 
subject  of  this  second  study  was  placed  in  the  New  England  Deaconess  Hos- 
pital, so  that  the  diet  was  under  rigid  control  throughout  the  entire  period. 
Being  a  medical  student  and  a  man  of  unusual  intellectual  keenness  in  the 
problems  involved,  he  cooperated  most  heartily  with  us  in  all  these  tests. 

A  series  of  nine  experiments  was  made  with  this  subject,  including  a  pre- 
liminary experiment  wdth  a  normal  diet,  five  experiments  "\;vT!th  a  carbohydrate- 
free  diet,  one  experiment  during  which  oatmeal  was  ingested,  one  experiment 
•vvdth  cane  sugar,  and  a  final  experiment  following  a  normal  diet.  The  vital 
statistics  of  the  subject  were  as  follows: 

Date  of  birth,  August  10,  1890;  height,  164  cm.;  range  in  body-weight 
during  experiments,  60.9  to  63.5  kilos. 


DISCUSSION    OF   RESULTS   AND   GENERAL   CONCLUSIONS.  129 

STATISTICS  OF  EXPERIMENTS  WITH  H.  H.  A. 
Respiration  Experiment  No.  1. 

Date,  December  27,  1911.     Body-weight  without  clothing,  63.5  kilos. 

The  diet  on  the  day  preceding  the  study  was  a  mixed  diet.  Breakfast: 
coffee,  with  sugar,  fried  potatoes,  and  bread.  Dinner:  barley  soup,  potatoes, 
bread,  apple  pie,  coffee,  hard  candy.  Supper:  fried  potatoes,  tea  -wath  sugar, 
bread,  and  a  few  dates. 

On  the  experimental  day  the  subject  came  to  the  laboratory  without 
breakfast  and  lay  down  upon  the  couch  at  8  a.  m.  The  experiment  began  at 
8''  50""  a.  m.,  continued  for  four  15-minute  periods  with  intervals  of  8  to  10 
minutes,  and  ended  at  10^  18"^  a.  m.  The  pulse-rate  ranged  from  74  to  82. 
The  subject  urinated  before  the  experiment  at  7  a.  m.,  and  after  it  was  over,  at 
lO"^  25""  a.  m.  A  sample  of  the  blood  was  taken  at  11''  10™  a.  m.  The  results 
of  the  experiment  may  be  found  in  table  138. 

Respiration  Experiment  No.  2. 

Date,  December  27,  1911.     Body-weight  without  clothing,  63.5  kilos. 

This  experiment  was  made  on  the  afternoon  of  the  day  of  the  preceding 
experiment,  being  the  first  with  a  carbohydrate-free  diet.  At  12  o'clock  noon 
the  subject  took  for  his  dinner  steak  and  butter,  ^vith  a  cupful  of  beef  tea.  The 
experiment,  which  consisted  of  two  15-minute  periods,  began  at  4''  38™  p.  m. 
and  ended  at  5*^  19™  p.  m.  The  pulse-rate  ranged  from  94  to  104.  After  the 
experiment  the  subject  ate  for  his  supper,  at  6  p.m.,  scrambled  eggs,  butter, 
and  tea  without  milk  or  sugar.  The  results  of  the  experiment  are  given  in 
table  138. 

Respiration  Experiment  No.  3. 

Date,  December  28,  1911.     Weight  without  clothing,  61.9  kilos. 

The  subject  came  to  the  laboratory  without  breakfast,  lay  down  upon  the 
couch  at  7*^  45™  a.  m.,  and  a  blood  sample  was  taken  about  8''  12™  a.  m.  The 
experiment  began  at  9  a.  m.,  continued  for  three  16-minute  periods,  and  ended 
at  lO*"  03™  a.  m.  The  pulse-rate  ranged  from  78  to  88.  The  subject  urinated 
at  lO''  35™  a.  m. 

The  diet  for  this  day  consisted  of  eggs,  butter,  and  coffee  at  12  o'clock; 
cheese,  fried  eggs,  bacon,  and  beef  tea  at  3  p.  m.,  and  lean  pork  chops  and  tea 
at  7''  30™  p.  m.     The  results  of  the  experiment  may  be  found  in  table  138. 

Respiration  Experiment  No.  4. 

Date,  December  29,  1911.     Body- weight  without  clothing,  61.3  kilos. 

Previous  to  the  experiment,  the  subject  said  he  felt  very  well,  fully  equal 
to  taking  a  long  walk.  He  came  to  the  laboratory  without  breakfast.  The 
experiment  began  at  8''  12™  a.  m.  and  continued  for  five  periods  of  15  to  16 
minutes  each.  The  subject  urinated  at  7  and  11''  25™  a.  m.  On  this  day  he 
ate,  at  12''  35™  p.  m.,  eggs  and  fried  ham,  with  weak  coffee;  at  3  p.  m.,  boiled 
scrod  with  butter,  and  beef  tea;  and  at  7  p.  m.,  fried  lamb  chops  and  tea.  The 
results  of  the  experiment  are  given  in  table  138. 

Respiration  Experiment  No.  5. 

Date,  December  30,  1911.     Body-weight  without  clothing,  61  kilos. 

No  breakfast  was  taken  by  the  subject  on  the  day  of  the  experiment.  The 
respiration  experiment  began  at  10''  46™  a.  m.  and  continued  for  one  8-minute 
and  two  15-minute  periods,  ending  at  12''  12™  p.  m.  The  pulse-rate  during  the 
experiment  ranged  from  67  to  78.  The  subject  urinated  at  7  a.  m.  and  12''  30™ 
p.  m.     He  took  food  during  the  day  as  follows:  1''  10™  p.  m.,  scrambled  eggs, 


130  METABOLISM   IN    SEVERE   DIABETES. 

butter,  cheese,  and  beef  tea;  3^  30""  p.m.,  beefsteak  and  butter;  7^  30°*  p.  m., 
boiled  chicken,  butter,  and  eggs.  The  results  of  the  experiment  are  included 
in  table  138. 

Respiration  Experiment  No.  6. 

Date,  December  31,  1911.     Body-weight  without  clothing,  61  kilos. 

As  usual,  the  subject  fasted  for  12  or  more  hours  previous  to  the  experi- 
ment. He  lay  down  upon  the  couch  at  8^  04°*  a.  m.,  the  experiment  beginning 
at  9^  01°*  a.  m.  The  measurements  were  made  in  three  15-minute  periods, 
ending  at  10^  30"*  a.  m.  The  pulse-rate  during  the  experiment  ranged  from  75 
to  83. 

During  the  day  the  subject  ate  as  follows:  At  1  p.  m.,  boiled  eggs,  includ- 
ing a  little  of  the  whites,  butter,  and  cream  (32  per  cent  fat)  with  soda;  at 
3^30°*  p.  m.,  eggs  (yolks  only),  bacon,  and  beef  tea;  at  7**  30"*  p.  m.,  eggs 
(yolks),  olive  oil,  cream  with  soda,  and  tea.  He  said  subsequently  that  he  felt 
very  thirsty  on  this  day,  and  drank  considerable  water,  but  this  did  not  affect 
the  volume  of  the  urine.     Table  138  gives  the  results  of  the  experiment. 

Respiration  Experiment  No.  7. 

Date,  January  1,  1912.     Body-weight  without  clothing,  60.9  kilos. 

The  experiment  was  divided  into  two  sections  with  an  interval  of  some  3 
hours;  in  the  first  part  the  subject  fasted  for  three  periods;  shortly  before  the 
second  part  of  the  experiment  began  he  ate  a  considerable  amount  of  oatmeal 
and  eight  periods  followed,  an  additional  portion  of  oatmeal  being  taken  before 
the  last  two  periods. 

The  subject  lay  down  upon  the  couch  at  7^*  45°*  a.  m.,  and  the  experiment 
began  at  8**  22°*  a.  m.  The  fasting  periods  ended  at  9^  51°*  a.  m.  At  12**  12°* 
p.  m.,  the  subject  took  582.8  grams  of  cooked  oatmeal,  83.6  grams  of  butter, 
and  400  c.c.  of  water.  The  following  six  15-minute  periods  began  at  12**  41" 
p.  m.  and  ended  at  4**  18°*  p.  m.  At  4^  35"*  p.  m.  the  subject  ate  a  second  por- 
tion of  oatmeal  (350.7  grams)  and  butter  (65.1  grams)  and  drank  400  c.c.  of 
water.  The  two  last  periods  of  the  experiment  began  at  5^  23°*  p.  m.,  and 
ended  at  6  p.  m.  In  the  first  period  after  food,  the  subject  probably  went  to 
sleep  for  a  moment  or  so.  In  the  final  period  he  coughed  during  the  last 
minute  of  the  experiment.  The  times  of  urinating  were  7  a.  m.,  10**  15°*  a.  m., 
11^  55°^  a.  m.,  3^  05"*  p.  m.,  and  6**  15°*  p.  m.  The  pulse-rate  during  the  fast- 
ing periods  ranged  from  76  to  84,  while  during  the  periods  following  the  inges- 
tion of  food  it  ranged  from  75  to  93.  The  measurements  of  the  metabolism 
are  given  in  table  138. 

Respiration  Experiment  No.  8. 

Date,  January  2,  1912.     Body-weight  without  clothing,  61.2  kilos. 

This  experiment  was  divided  into  two  sections,  the  first  three  periods 
being  fasting,  and  the  last  six  periods  following  the  ingestion  of  cane  sugar. 
For  supper  the  night  preceding  the  experiment  the  subject  took  coffee  with 
sugar,  and  bread. 

The  fasting  periods  began  at  7**  42°*  a.  m.  and  ended  at  8**  45°*  a.  m.  At 
9**  12°*  a.  m.,  the  subject  took  100  grams  of  cane  sugar  in  400  c.c.  of  water  and 
lemon  juice.  The  following  periods  began  at  9^  22"*  a.  m.,  ending  at  12^  57°* 
p.  m.  During  the  fasting  periods  the  pulse-rate  ranged  from  64  to  68;  in  the 
periods  following  the  taking  of  the  cane  sugar  it  ranged  from  73  to  86.  The 
subject  urinated  at  10>*  30"*  a.  m.,  also  urinated  and  defecated  between  the 
eighth  and  ninth  periods,  resting  afterwards  for  about  15  minutes.  The 
results  of  the  experiment  are  to  be  found  in  table  138. 


DISCUSSION   OF   RESULTS   AND    GENERAL   CONCLUSIONS. 


131 


Respiration  Experiment  No.  9. 

Date,  January  3,  1912.     Body-weight  without  clothing,  62.5  kilos. 

After  leaving  the  laboratory  at  1  p.  m.,  January  2,  the  subject  drank,  at 
1^30™  p.  m.,  two  cupfuls  of  coffee  with  sugar  and  ate  an  egg  sandwich.  At  6 
p.  m.  he  took  beef  stew  with  potatoes,  bread,  coffee,  rice  pudding,  and  apple  pie. 
Table  138. — Results  of  respiration  experiments  Nos.  1  to  9  with  H.  H.  A. 


Experi- 
ment 
No. 

Date. 

Diet  and  time. 

Duration. 

Carbon 

dioxide 

eUminated 

per  minute. 

Oxygen 
absorbed 
per  minute. 

Respiratory 
quotient. 

Average 
pulse-rate. 

Average 
respiration- 
rate. 

Normal. 

1911. 

Without  food: 

min.   sec. 

c.c. 

c.c. 

1 

Dec.  27.. 

S'' 50™  a.m.... 

14  23 

208 

225 

0.93 

76 

12 

9  13  a.m.... 

14  19 

208 

223 

.93 

77 

11 

9  37  a.m.... 

14  16 

193 

228 

.85 

78 

12 

10  02  a.m.... 

15  30 

195 

221 

.88 

79 

13 

Average 

201 

224 

.90 

78 

12 

Carbohydrate-free. 

With  food:' 

2 

Dec.  27.. 

4'>38"p.m.... 

14  54 

205 

289 

.71 

98 

14 

5  04  p.m.... 

14  46 

209 

290 

.72 

102 

12 

Without  food: 

3 

Dec.  28.. 

g'' 00™  a.m.... 

15  55 

189 

263 

.72 

83 

11 

9  22  a.m.... 

15  52 

187 

250 

.75 

81 

14 

9  47  a.m.... 

15  51 

195 

262 

.74 

84 

12 

Average 

190 

258 

.74 

83 

12 

4 

Dec.  29.. 

81^  12™  a.m.... 

is  28 

176 

262 

.67 

73 

12 

8  38  a.m.... 

15  52 

176 

273 

.65 

74 

11 

9  05  a.m.... 

15  48 

177 

247 

.72 

73 

10 

9  59  a.m.... 

15  37 

183 

264 

.69 

74 

10 

10  48  a.m.... 

15  05 

184 

246 

.75 

74 

12 

Average 

179 

258 

.70 

74 

11 

5 

Dec.  30.. 

10»>46™a.m.... 

7  44 

185 

250 

.74 

69 

11 

11  03  a.m.... 

14  58 

171 

237 

.72 

70 

10 

11  57  a.m.... 

15  05 

177 

235 

.75 

72 

9 

Average 

178 

241 

.74 

70 

10 

6 

Dec.  31.. 

gl'Ol^a.m.... 

i4  35 

169 

242 

.70 

79 

14 

9  35  a.m.... 

14  39 

175 

238 

.73 

80 

14 

10  16  a.m.... 

14  22 

175 

246 

.71 

77 

13 

1912. 

Average 

173 

242 

.71 

79 

14 

7 

Jan.  1.... 

S*- 22™  a.m.... 

ii  40 

162 

240 

.67 

81 

14 

9  07  a.m.... 

14  49 

160 

233 

.69 

77 

14 

9  36  a.m.... 

15  05 

169 

243 

.70 

79 

13 

Average 

164 

239 

.69 

79 

14 

Oatmeal  and  butter. 

With  food: 

12h41™p.m.2.. 

14  52 

180 

267 

.67 

84 

16 

1  08  p.m.... 

15  07 

192 

275 

.70 

86 

16 

1  41  p.m 

15  12 

199 

275 

.72 

82 

15 

2  08  p.m.... 

15  39 

204 

274 

.74 

92 

16 

3  33  p.m.... 

15  13 

207 

283 

.73 

85 

11 

4  04  p.m.... 

14  12 

186 

254 

.73 

77 

13 

5  23  p.m.3.. 

15  02 

208 

284 

.73 

82 

13 

5  45  p.m 

14  42 

211 

291 

.72 

84 

14 

Without  food: 

8 

Jan.  2.... 

7'>42™a.m.... 

14  27 

158 

223 

.71 

67 

11 

8  05  a.m.... 

15  16 

146 

208 

.70 

65 

13 

8  29  a.m.... 

15  41 

156 

215 

.73 

67 

11 

Average 

153 

215 

.71 

66 

12 

Cane  sugar. 

With  food:< 

9'»22™a.m.... 

14  01 

209 

241 

.87 

73 

11 

9  45  a.m.... 

14  09 

242 

232 

1.04 

79 

15 

10  14  a.m.... 

14  28 

238 

245 

.97 

76 

15 

11  05  a.m.... 

15  08 

229 

247 

.93 

80 

15 

11  34  a.m.... 

14  32 

201 

241 

.83 

85 

14 

12  41  p.m.... 

14  30 

173 

230 

.75 

80 

12 

Normal. 

Without  food: 

0 

Jan.  3.... 

7'' 5.?°  a.m.... 

16  04 

172 

216 

.79 

74 

10 

8  24  a.m.... 

15  05 

169 

212 

.80 

73 

8 

Average 

171 

214 

.80 

74 

9 

1  Subject  ate  169  gms.  beefsteak,  14.5  gms.  butter,  and  1  cup  beef  tea  at  12  noon. 
'Subject  ate  582.8  gms.  cooked  oatmeal  and  83.6  gms.  butter  at  U/'  12™  p.m. 
'Subject  ate  350.7  gms.  cooked  oatmeal  and  65.1  gms.  butter  at  4''  3-5™  p.m. 
<  Subject  took  100  gms.  cane  sugar  in  400  c.c.  of  water  with  juice  oi  lemon  at  9"  12™  a.m. 


132 


METABOLISM   IN   SEVERE   DIABETES. 


On  the  experimental  day  the  subject  came  to  the  laboratory  fasting,  and 
the  experiment  began  at  7^  55™  a.  m.,  continuing  for  two  periods  of  approxi- 
mately 15  minutes  each  and  ending  at  S^  39™  a.  m.  During  the  experiment 
the  pulse-rate  ranged  from  72  to  75.  The  measurements  of  the  metabolism 
are  given  in  table  138. 

RESULTS  OF  EXPERIMENTS  WITH  H.  H.  A. 

The  measurements  of  the  total  metabolism  of  the  subject  for  the  whole 
series  of  experiments  are  given  in  table  138.  Previous  to  the  first  experiment 
the  subject  had  been  on  a  normal  diet,  but  fasted  for  some  12  hours  before  com- 
ing to  the  laboratory.  Under  these  conditions  he  absorbed  about  225  c.c.  of 
oxygen  per  minute  and  had  an  average  pulse-rate  of  approximately  78.  On 
the  morning  follo-wdng  the  carbohydrate-free  diet,  the  oxygen  absorption  was 
increased  to  approximately  255  c.c.  per  minute,  and  the  pulse-rate  to  83.  On 
the  next  four  days  of  the  carbohydrate-free  diet,  the  metabolism  remained 
high,  although  there  was  a  tendency  for  it  to  approximate  more  nearly  the 
normal  level  as  the  experiment  progressed.  Singularly  enough,  notwithstand- 
ing the  high  metabolism,  the  pulse-rate  on  the  first  two  days  was  considerably 
below  that  on  the  normal  day.  Unfortunately  simultaneous  observations 
•with  regard  to  the  blood-pressure  were  not  obtained. 


Table  139.- 

—Statistics  of 

urine 

— Subject 

H.H 

.A. 

Date. 

.i 

3 

"o 
o 

s 

3 
1 

1 

u 

us 

o 

a 

i 

1 
o 

01 

M 
5 

-d 

1 
o 

■a 

1 
1 

i 

1 

Ammonia. 

1 

>>2 
.2  6 

< 

Diet. 

1 

11 

1911. 
Dec.  25-26. 
Dec.  26-27. 
Dec.  27-28. 
Dec.  28-29. 
Dec.  29-30. 
Dec.  30-31. 
Dec.  31-\ 
Jan.      1  /•• 

1912. 
Jan.      1-  2. 
Jan.     2-  3. 
Jan.      3-  4. 

C.C. 

1245 
1974 
1667 

985 
1304 

928 

880 

991 
818 
648 

1.0155 

1.013 

1.018 

1.0285 

1.026 

1.0265 

1.026 

1.016 
1.0165 
1.023 

Pale 

Acid. 

gma. 

gms. 
10.22 
9.39 
11.82 
16.45 
21.28 
17.52 

14.63 

8.72 
6.62 

7.18 

gms. 

0.88 
.87 
.56 

1.0 

1.27 

1.62 

1.93 

1.75 
1.29 

p.ct. 
7.1 
7.6 
3.9 
5.0 
4.9 
7.6 

10.9 

16.5 
16.0 

gms. 
11.6 
20.9 
14.0 
8.6 
6.3 
7.1 

5.8 

174.3 
197.4 
100.0 
384.1 
326.0 
352.6 
423.6 

297.0 
237.2 
194.4 

Normal. 

Do. 
Carbohydrate-free 

Do. 

Do. 

Do. 

Do. 

Oatmeal.' 
Cane  sugar.' 
Normal. 

Slightly  pale. 

Normal 

Normal 

Pale 

Normal 

Normal 

Pale  .. 

Acid. 

Acid. 

Acid. 
Acid. 
Acid. 

0 
0 

Acid. 

Acid. 
Acid, 

0 

0 
0 

4.8 

Pale 

'Sugar  and  albumen  tested  tor  each  day  and  uniformly  absent. 

'Subject  ate  582.8  gms.  cooked  oatmeal  and  83.6  gms.  butter  at  12.12  p.m.:  also  350.7  gms.  cooked  oatmeal  and  65.1 
gms.  butter  at  4.35  p.m.     See  statistics  of  experiment  No.  7. 

'Subject  took  100  gms.  cane  sugar  in  400  c.c.  of  water  with  juice  of  lemon  at  9.12  a.m.  For  diet  rest  of  day  see  sta- 
tistics of  experiments  Nos.  8  and  9. 

Urine  analyses. — The  urine  was  collected  in  24-hour  periods  from  Decem- 
ber 25  to  January  4,  although  on  certain  days  the  determinations  were  made  in 
periods  corresponding  to  the  experimental  periods.  The  results  of  the  urine 
analyses  are  given  in  table  139.  Only  one  determination  of  the  /3-oxybutyric 
acid  was  made,  i.  e.,  on  the  fifth  day  of  the  carbohydrate-free  diet,  and  4.8 
grams  of  /3-oxj^butyric  acid  were  found.  There  was  no  diacetic-acid  reaction, 
but  the  percentage  of  ammonia-nitrogen  to  total  nitrogen  was  somewhat  higher 
than  normal,  if  not  excessively  high.  On  the  oatmeal  and  cane-sugar  days 
following  the  carbohydrate-free  diet,  the  percentage  of  ammonia-nitrogen  in 


DISCUSSION   OF   RESULTS   AND    GENERAL   CONCLUSIONS. 


133 


the  proportion  of  total  nitrogen  increased  considerably,  this  being  largely  due 
to  the  fact  that  there  was  a  decided  decrease  in  the  total  nitrogen.  Sugar  and 
albumen  were  tested  for  each  day  and  were  uniformly  absent. 

The  general  picture  of  the  urine  analyses  with  this  subject  does  not  by  any 
means  indicate  as  striking  an  acidosis  as  was  found  with  subject  H.  L.  H.  On 
the  other  hand,  it  is  reasonably  clear  from  the  presence  of /3-oxy butyric  acid  that 
there  was  an  acidosis,  and  that  this  was  due  to  the  carbohydrate-free  diet. 
The  absence  of  the  determinations  of  /3-oxybutyric  acid  on  the  other  days  is 
much  to  be  regretted. 

The  alkali  retention  by  the  kidney,  which,  taken  together  with  the 
ammonia  excretion,  makes  up  the  protective  mechanism  of  the  body  against 
acidosis,  shows  an  increase  during  the  days  of  carbohydrate-free  diet  and  a 
return  toward  normal  with  the  addition  of  carbohydrates  to  the  food,  fol- 
lowing closely  the  ammonia  curve.^ 

Table  140. — Determinations  made  on  alveolar  air  with  H.  H.  A. 


Date. 

Carbon  dioxide. 

Remarks. 

Date. 

Carbon  dioxide. 

Remarks. 

Per 
cent. 

Tension. 

Per 
cent. 

Tension. 

1911. 
Dec.  26 .  . . 

Av.... 
Dec.  28... 

Av.... 
Dec.  29... 

.5.62 
5.4.3 
5.46 
5.68 
5.94 
5.60 

mm. 

At  about  3  p.m.;  prob- 
ably     food      taken 
about  noon. 

About  10'>45™  a.m.:  be- 
fore eating. 

1911. 
Dec.  31.... 

Av.... 

1912. 
Jan.  1 

4.70 
4.64 
4.53 
4.69 

mm. 

About  11  p.m.;  before 
eating. 

About  10  a.m.;  before 
eating. 

At  2''  30"  p.m.;  after 
oatmeal  and  butter 
at  12'"  12™  p.m. 

At  6''  15"   p.m.   after 
oatmeal  and  butter 
at  4''  35"  p.m. 

4.64    1      33.2 

5  62 

40  1 

4.34 
4.53 
4.39 
4.75 
4.56 
4.76 
4.70 

5.11 
5.04 
5.00 

. . . . 

... 

5  05 

35.6 

4.81 
4.67 
4.66 
4  85 

fore  eating.                   {           Av 

4.58    1      32.6 

Aboutl2''15'"p.m.;  be- 
fore eating. 

Jan.  1 

Av.... 
Jan.  1 

Av. . . . 

5.27 
5.18 

Av.... 

4  75 

33.9 

5.23    1      37.2 

4.54 
4.85 
4.79 
4.87 

5.10 

5.02  1       .... 

5.03  1       .... 

Av.... 

4.76 

34.4 

5.05          36.0 

Composition  of  the  alveolar  air. — Determinations  of  the  alveolar  air,  with 
particular  reference  to  the  carbon-dioxide  percentage  and  tension,  were  made 
on  a  number  of  days  throughout  this  test.  The  results  are  presented  in  table 
140.  The  normal  value  found  when  the  subject  began  the  carbohydrate-free 
diet  was  5.62  per  cent  of  carbon  dioxide,  corresponding  to  about  40.1  mm.  ten- 
sion. With  the  carbohydrate-free  diet  this  tension  dropped  almost  immedi- 
ately, and  reached  its  minimum  on  the  fifth  daj',  32.6  mm.  On  the  resumption 
of  a  normal  diet  with  oatmeal  there  was  an  immediate  response  and  an  increase 


'H.  M.  Adier  and  G.  Blake,  Archives  of  Internal  Medicine,  1911,  7,  p.  479. 


134 


METABOLISM   IN    SEVERE   DIABETES. 


in  the  carbon-dioxide  tension  to  37.2  mm.  The  correlation,  therefore,  between 
the  carbon-dioxide  tension,  the  alveolar  air,  the  total  metabolism  and  the 
acidosis  is  clearly  shown. 

Blood  examination. — The  blood  was  examined  daily  and  the  results  are 
reported  in  table  141. 

Table  141. — Results  of  blood  examinations^ — Subject  H.  H.  A. 


Date  and  time. 

Time  after 
last  meal. 

Hemo- 
globin 
(Fleischl). 

White 
blood- 
corpuscles. 

Rod  blood- 
corpuscles. 

Dec.  27,  1911: 

4"  00™  p.m 

Dec.  28,  1911: 

8^  12™a.m 

4    00    p.m 

Dec.  29,  1911: 

4*' 00™  p.m 

Dec.  30,  1911: 

4'"  00™  p.m 

hrs.  min. 
i      0 

14      0 
1      0 

1      0 

30 

p.  ct. 
95 

96 
95 
96 

17,300 

10,600 
11,100 

11,700 

8.000 

5,860,000 

5.'676.bbb 
5,864.000 
6,128,000 

'  On  Dec.  28  a  stained  specimen  of  the  blood  was  examined  microscopically  with  the  following  result:  Differ- 
ential count  of  200  white  blood-corpuscles  showed  polynuclear  leucocytes  82.5  per  cent,  lymphocytes 
15.5  per  cent, transitionals  1  per  cent.eosinophiles  1  percent.  The  red  blood-corpuscles  showed  nothing 
abnormal. 

It  will  be  seen  that  the  hemoglobin  was  constant  for  the  four  days;  the 
number  of  red  blood- corpuscles  was  also  essentially  constant.  We  are  unable 
to  explain  the  increase  in  the  number  of  white  blood-corpuscles  on  the  first 
afternoon  after  the  first  carbohydrate-free  meal.  The  slight  decrease  in  the 
white  blood-corpuscles  found  for  the  following  successive  days  does  not  warrant 
conclusions,  particularly  without  support  from  similar  experiments. 

The  differential  count  of  the  white  blood-corpuscles  shows  nothing 
abnormal. 

RELATIONS  BETWEEN  A  NORMALLY  INDUCED  ACIDOSIS  AND  THE  OBSERVED 
INCREASE  IN  THE  METABOLISM  IN  SEVERE  DIABETES. 

With  both  of  these  subjects  there  was  a  noticeable  increase  in  the  total 
metabolism  as  measured  by  the  oxygen  consumption,  coincident  with  the  use 
of  a  carbohydrate-free  diet.  With  one  case  at  least  there  was  a  corresponding 
increase  in  the  pulse-rate,  while  with  the  other  there  was  a  temporary  increase 
in  the  pulse-rate,  followed  by  a  decline.  Since  it  is  probable  that  an  intimate 
relationship  exists  between  the  blood-pressure  and  the  pulse-rate,  we  have  every 
reason  to  believe  that  if  all  the  data  had  been  available  this  seeming  discrep- 
ancy between  the  results  with  the  two  subjects  could  be  readily  explained. 

If  the  presence  of  the  small  amount  of  /3-oxybutyric  acid  found  with  these 
subjects  was  sufficient  to  stimulate  the  metabolism  so  that  the  metabolic 
activity  of  the  body  itself  as  a  whole  was  increased  by  the  amount  here  found, 
it  is  not  at  all  surprising  that  in  severe  diabetes  the  same  processes  which 
involved  the  formation  and  circulation  of  j3-oxybutyric  acid  molecules  would 
likewise  tend  to  stimulate  the  body  activity  of  the  diabetic.  On  the  other 
hand,  the  constant  presence  of  j8-oxybutyric  acid  throughout  a  long  period  of 
time  during  the  course  of  the  disease  might  easily  lead  to  an  acquired  tolerance 
for  the  presence  of  j8-oxybutyric  acid  which  would  involve  the  necessity  for  the 


DISCUSSION   OF   RESULTS   AND   GENERAL   CONCLUSIONS.  135 

presence  of  a  very  much  larger  amount  of  the  acid  in  order  to  produce  a  given 
stimulating  effect. 

In  a  recently  concluded  experiment  with  a  fasting  man  in  this  laboratory, 
after  31  days  of  fasting  it  was  found  that  the  amount  of  /J-oxybutyric  acid  in 
the  urine  was  not  materially  greater  than  that  found  with  these  two  subjects 
when  they  were  subsisting  upon  a  carbohydrate-free  diet.  There  was,  how- 
ever, no  measurable  increase  in  the  metabolism  noted  with  this  subject;  on  the 
contrary  there  was  a  marked  decline  in  total  metabolism  as  the  fast  progressed. 
"While,  therefore,  it  would  appear  possible  to  explain  the  increased  metabolism 
noted  with  diabetics  upon  the  ground  that  the  severity  of  the  acidosis  caused 
an  increased  metabolism,  we  can  at  present  only  state  the  fact  that  coincidental 
with  the  severe  acidosis  there  was  found  an  increased  metabolism.  Whether 
the  presence  of  /3-oxybutyric  acid  molecules  passing  through  the  blood  stimu- 
lates the  cell  activity,  or  whether  the  decrease  in  the  alkalescence  of  the  blood 
produces  a  similar  effect,  we  can  not  at  present  state.  Whatever  the  effect,  the 
body  probably  to  a  certain  extent  may  accustom  itself  to  this  stimulus  and  thus 
react  less  as  time  goes  on.  The  fact  that  there  may  be  55  grams  or  more  of 
/3-oxybutyric  acid  excreted  per  day  with  diabetics,  with  no  greater  increase  in 
the  metabolism  above  normal  than  the  increase  found  with  a  normal  individual 
subsisting  on  a  carbohydrate-free  diet,  who  had  but  4  or  5  grams  of  /3-oxy- 
butyric acid,  would  imply  that  as  the  disease  progressed  from  day  to  day,  the 
body  became  accustomed  to  the  specific  stimulus  (probably  the  presence  of 
acid)  and  responded  less  and  less.^ 

Clinical  experience  with  diabetic  patients  suggests  that  an  acid  intoxica- 
tion of  moderate  severity  suddenly  produced  by  the  withdrawal  of  carbo- 
hydrates is  more  dangerous  than  a  much  more  severe  acidosis  produced  by  a 
gradual  withdrawal  of  carbohydrates.  Thus  the  sudden  withdrawal  of  carbo- 
hydrates from  diabetic  patients  upon  entrance  to  hospitals  may  result  in  the 
acute  onset  of  coma.  It  is  often  a  surprise  to  find  that  in  the  urines  of  such 
patients  the  quantity  of  acid  is  so  small.  In  contrast,  cases  of  severe  diabetes 
subjected  to  marked  restriction  of  carbohydrates  for  a  long  period  may  present 
an  acidosis  of  severe  degree  amounting  to  even  50  grams  of  /3-oxybutyric  acid 
daily,  and  yet  show  no  inconvenience  therefrom.  In  these  cases  the  acidosis 
apparently  greatly  exceeds  for  weeks  at  a  time  the  acidosis  of  the  former  group 
of  cases. 

'Roily  {loc.  cit.),  noting  that  the  high  oxygen  consumption  observed  when  patients  first 
came  to  the  hospital  was  frequently  lowered  by  dietetic  treatment,  infers  that  this  can  not 
be  explained  alone  by  the  reduction  in  protein  ingestion,  but  that  the  previous  high  oxygen 
consumption  must  be  due  to  improper  diet,  exercise,  consumption  of  food,  or  other  causes 
as  yet  unknown. 

Leimdorfer  {loc.  cil.)  maintains  that  the  increased  metabolism  of  severe  diabetes  is 
caused  for  the  greater  part  by  an  increase  in  the  intermediary  metaboUc  processes,  such  as 
the  formation  of  sugar  and  acetone  bodies  from  protein  and  fat.  A  small  part  is  due  to  the 
increased  work  of  respiration. 

As  the  page  proof  of  this  publication  leaves  our  hands,  we  note  that  Grafe  and  Wolf 
(Deutsch.  Archiv  f.  klin.  Med.,  1912,  107,  p.  227)  probably  have  evidence  in  regard  to  the 
increased  metabolism  in  severe  diabetes  as  a  later  communication  is  promised. 


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